Non-coding RNAs regulate autophagy in kidney disease: friend or foe?

Yankun Li; Tongtong Ma; Xinhua Liang; Tingting Jin; Xingqi Zhao; Junmin Huang; Junfeng Hao; Huafeng Liu; Peng Wang

doi:10.1080/15548627.2025.2551683

. 2025 Sep 15;21(12):2537–2560. doi: 10.1080/15548627.2025.2551683

Non-coding RNAs regulate autophagy in kidney disease: friend or foe?

Yankun Li ^a,^*, Tongtong Ma ^b,^*, Xinhua Liang ^a, Tingting Jin ^c, Xingqi Zhao ^d, Junmin Huang ^a, Junfeng Hao ^a, Huafeng Liu ^a, Peng Wang ^a,^✉

PMCID: PMC12758291 PMID: 40851276

ABSTRACT

Macroautophagy/autophagy is a conserved cellular process that degrades misfolded proteins and damaged organelles to regulate cell survival and division. Normal levels of autophagy are observed in healthy kidney cells. In contrast, excessive or insufficient autophagy is observed during kidney disease progression. However, canonical treatments that regulate autophagy using chemical reagents may induce unexpected side effects in other organs. This necessitates the development of therapeutic approaches with fewer adverse effects. Non-coding RNAs, which are highly tissue-specific, regulate autophagy and accurately modulate the expression of related genes. This review presents evidence of the effects of non-coding RNAs on the progression of kidney diseases and their responses to treatment in vitro, in vivo, and in clinical trials. Our analyses and interpretations of key findings elucidate the pathogenesis of kidney diseases and explore potential new therapeutic approaches.

Abbreviations: 3' UTR: 3' untranslated region; 3-MA: 3-methyladenine; ADPKD: autosomal dominant polycystic kidney disease; AKI: acute kidney injury; ccRCC: clear cell RCC; ATG: autophagy related gene; ceRNA: competing endogenous RNA; circRNA: circular RNA; CKD: chronic kidney disease; DKD: diabetic kidney disease; HG: high glucose; IRI: ischemia-reperfusion injury; lncRNA: long non-coding RNA; LPS: lipopolysaccharide; miRNA: microRNA; MTOR: mechanistic target of rapamycin kinase; ncRNA: non-coding RNA; PI3K: phosphoinositide 3-kinase; RCC: renal cell carcinoma; ROS: reactive oxygen species; RTEC: renal tubular epithelial cells; ULK1: unc-51 like autophagy activating kinase 1; UUO: unilateral ureteral obstruction; VHL: von Hippel-Lindau tumor suppressor.

KEYWORDS: circRNA, kidney disease, lncRNA, miRNA, precision medicine, therapeutic targets

Introduction

The global prevalence of kidney disease surpasses that of all other non-communicable diseases. The death rate of kidney disease has continuously increased over the past two decades [1]. Furthermore, renal cell carcinoma (RCC) accounts for approximately 3.8% of all newly identified cancers. Clear cell RCC (ccRCC), which primarily stems from renal tubular epithelial cells (RTECs), remains the predominant RCC subtype at approximately 85% [2–4]. Moreover, kidney dysfunction is the seventh leading cause of mortality worldwide, and its prevalence is projected to continuously increase. The progression of renal failure is postponed through kidney replacement therapy, which has substantial economic implications. However, up to 98% of individuals in need of this therapy may lack treatment access in resource-limited settings [5].

Oxidative stress, profibrotic cytokines, urinary proteins, inflammation, and aging play crucial roles in kidney disease [6–8]. Therefore, cellular energy homeostasis is frequently compromised during disease onset and progression. This leads to the initiation of autophagy in renal cells [9–11]. Successful autophagy effectively promotes energy proficiency through ATP production. In addition, it modulates cell and wound repair by removing damaged or redundant organelles and proteins to ameliorate kidney disease [6,12]. However, sustained autophagy activation in injured RTECs may lead to renal fibrosis after acute kidney injury (AKI) [13,14]. Protein kinase inhibitors, such as rapamycin and 3-methyladenine (3-MA), modulate renal autophagy to control kidney disease progression [15,16]. Nevertheless, the regulation of autophagy via chemical treatments that target molecules upstream of this highly conserved cellular recycling process may cause adverse effects in many cells.

The kidney’s high metabolic demand renders it particularly vulnerable to autophagic dysregulation. Emerging evidence implicates non-coding RNAs (ncRNAs) as master regulators of autophagy, fine-tuning disease progression through epigenetic, transcriptional, and post-transcriptional mechanisms. Unraveling these interactions may unlock novel strategies to overcome the limitations of conventional autophagy-targeted therapies.

ncRNAs are a cluster of transcripts that account for > 98% of the genome. They mainly include microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA). miRNAs are highly conserved among various species. The inhibitory effect of MIR30A on BECN1 expression, which leads to decreased autophagy, has been demonstrated in cancer cells [17]. Furthermore, high-throughput sequencing technology has facilitated the identification of lncRNAs and circRNAs. lncRNAs display remarkable spatiotemporal characteristics, especially those characterized by tissue specificity [18,19]. For example, lncRNA MEG3 activates autophagy and promotes cellular growth in bladder cancer [20]. circRNAs derive stability from their closed circular structure. circHIPK2 combines autophagy and endoplasmic reticulum (ER) stress interactions to activate astrocyte activation [21]. The regulatory role of ncRNAs in autophagy has been shown in kidney diseases. Therefore, this review outlines the mediatory roles of miRNAs, lncRNAs, and circRNAs in autophagy, which aggravates or mitigates the progression of kidney diseases.

The definition and diverse mechanisms of ncRNAs

Although incapable of protein-coding, ncRNAs exert considerable control over cellular structures. These important regulators of autophagy help maintain cellular balance. In addition, ncRNAs can be categorized into two primary groups based on their regulatory roles: housekeeping and regulatory [22–24]. Housekeeping ncRNAs are widely expressed in cells. They modulate general cellular functions and play essential roles in cell viability [25,26]. In contrast, regulatory ncRNAs are regarded as the main RNA molecules that modulate gene expression. They regulate gene expression at the epigenetic, transcriptional, and post-transcriptional levels [27,28].

Figure 1 illustrates the classification of ncRNAs. In this review, we focus on the following regulatory ncRNAs: miRNAs, lncRNAs, and circRNAs.

miRNAs

miRNAs comprise 17–25 nucleotides and mainly exert their effects post-transcriptionally [29]. In addition, they are key parts of RNA interference. miRNAs interact with their target mRNAs by forming bases at the 3' untranslated region (3' UTR) [30]. This leads to the degradation or translational suppression of target genes. The miRNA-induced silencing complex interacts with specific mRNAs through miRNA response elements in the 3' UTR. These response elements act as matching sequences to the 2–8 nucleotides at the 5' terminus of miRNA.

lncRNAs

lncRNAs are transcripts longer than 200 nucleotides. They intricately control gene activity at various stages, including chromatin modification, transcriptional control, and post-transcriptional regulation. The functions of lncRNAs depend on their subcellular localization [31], which can be nuclear or cytoplasmic. lncRNAs regulate the transcription of both cis- and trans-acting genes in the nucleus. Thus, they contribute to chromatin remodeling and post-transcriptional gene regulation. Contrastingly, lncRNAs affect protein localization, regulate mRNA synthesis, stabilize mRNA, and modulate protein-protein interactions in the cytoplasm [32,33].

circRNAs

circRNAs are formed through back-splicing, a process in which the 5' and 3' ends of the RNA molecule bond covalently to create a stable circular structure [34]. They play diverse regulatory roles in molecular interactions [35]. circRNAs act as molecular sponges. Specifically, they serve as competing endogenous RNAs (ceRNAs) by sequestering miRNAs. This process modulates the availability of miRNAs for target mRNAs, ultimately influencing disease progression. circRNAs can also bind directly to mRNA molecules [36], further regulating their functions. They also interact with proteins [37], including those that bind RNA, which influences their roles in cellular processes. Moreover, circRNAs interact with transcription factors [38], which consequently affects the regulation of specific genes. Even circRNAs can encode functional proteins [39].

Autophagy

Classification

Autophagy is a cellular process that degrades and recycles damaged or unnecessary cellular components. It is categorized based on how the intracellular substrate is delivered to the lysosomal cavity: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA) [40]. Microautophagy is a rapid form of autophagy that does not form autophagosomes. Instead, it occurs through direct degradation by lysosomes or late endosomes. During this process, the lysosomal membrane folds inward to surround cellular components like parts of the mitochondrion or ER [41]. CMA is highly selective; it recognizes and binds proteins with specific sequences through molecular chaperones [42]. These proteins are then transported into lysosomes by transport proteins on the lysosomal membrane for degradation [43].

Macroautophagy is categorized as either nonselective or selective, based on the specificity of the degraded substrate. Microautophagy can also be either nonselective or selective. Nonselective autophagy entails the random uptake of cytoplasmic material for degradation, while selective autophagy targets specific cellular components for degradation. Selective autophagy specifically targets and degrades various substrates, including mitochondria, peroxisomes, ribosomes, ER, lysosomes, nucleus, proteasomes, and lipid droplets [44,45].

The ncRNA regulation of microautophagy and CMA, especially in kidney disease, remains largely understudied. Therefore, this review primarily focuses on studies related to macroautophagy. In addition, this review mainly focuses on nonselective autophagy because it is more widely studied than selective autophagy.

Process

Macroautophagy, commonly known as autophagy, is the most extensively researched type and can be broadly categorized into the following stages:

Initiation: when the cell undergoes nutrient deficiency or stress, it activates a series of signaling pathways, such as inhibition of MTOR (mechanistic target of rapamycin kinase) and AMP-activated protein kinase (AMPK). These pathways activate ATG (autophagy autophagy related gene) proteins, including the ULK1 (unc-51 like autophagy activating kinase 1) complex, which initiates the autophagy process.
Nucleation and vesicle formation: regulated by the initiation signal, the cell membrane structure begins to form a double-membrane sequestering compartment, namely a phagophore. This process usually begins in the ER, and the phagophore gradually expands, enveloping the surrounding cytoplasm and organelles.
Expansion and maturation: phagophores continue to grow, ultimately sealing and forming double-membrane vesicle termed an auotophagosome. This compartment may fuse with other membrane structures, such as endosomes or lysosomes, eventually forming an autolysosome.
Degradation and recycling: mature autophagosomes fuse with lysosomes to form autolysosomes. After this fusion, enzymes within lysosomes degrade the autophagosomal membrane and cargo into basic biomolecules such as amino acids and fatty acids. These molecules are subsequently released back into the cytoplasm, where they can be reused by the cells and participate in new biosynthetic processes, completing the cycle of autophagy [46–49].

Signaling pathways on autophagy regulation

Autophagy is controlled by a sophisticated network of intracellular signals that react to nutrient availability. This network can either stimulate or inhibit autophagy. This action helps cells adapt to stress or counteract its effects. Key complexes involved in the regulation include MTOR, class III phosphatidylinositol3-kinase (PtdIns3K), ATG12–ATG5, and MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). The MTOR kinase is a vital regulator of autophagy. When activated by AKT and MAPK (mitogen-activated protein kinase) signaling, MTOR inhibits autophagy. Conversely, its negative regulation by AMPK and TP53/p53 signaling promotes autophagy [50]. The serine/threonine kinases ULK1, ULK2, and ULK3 act downstream of the MTOR complex and form a large complex with the mammalian homolog of ATG13 and the scaffold protein RB1CC1/FIP200 [51]. The PtdIns3K complex is essential for autophagy induction and includes PIK3C3/VPS34, BECN1 (a mammalian homolog of yeast Vps30/Atg6), PIK3R4/VPS15/p150, NRBF2 and either ATG14 or UVRAG. ATG12 conjugates to ATG5 through a ubiquitin-like reaction involving ATG7 and ATG10, and then forms a large complex with ATG16. LC3 is cleaved by ATG4 to produce cytosolic LC3-I, which conjugates to phosphatidylethanolamine (PE) through a ubiquitin-like reaction involving ATG7 and ATG3, forming lipidated LC3-II that attaches to phagophore membranes [52]. High MTOR activity inhibits autophagy under nutrient-rich conditions by phosphorylating ULK1 at Ser757, which disrupts the ULK1-AMPK interaction. In contrast, during starvation, AMPK directly activates ULK1 through phosphorylation at Ser317 and Ser777, promoting autophagy [53]. Autophagy is also induced by reactive oxygen species (ROS), ER stress, hypoxia, DNA damage, and immune signaling [54]. Activated ULK1 phosphorylates BECN1 on S14, enhancing the activity of the ATG14-containing PIK3C3/VPS34 complex and promoting phagophore formation. Subsequently, ATG genes control autophagosome formation through the ATG12–ATG5 and LC3-II complexes [55].

Other pathways that regulate autophagy include BCL2, which inhibits autophagy by suppressing BECN1 activation [56]. The RAS-RAF-MAP2K1/MEK-MAPK/ERK pathway inhibits autophagy by activating the mechanistic target of rapamycin kinase complex 1 (MTORC1) or promotes LC3-II expression and autophagy activation [57,58]. MAPK/p38 inhibits autophagy by suppressing ULK1 activation or promotes it by upregulating BECN1 and ATG7 expression [59,60]. The WNT-CTNNB1/β-catenin pathway indirectly inhibits autophagy by suppressing LC3-II and BECN1 expression [61]. TP53 promotes autophagy by enhancing the transcription and synthesis of autophagy-related proteins [62]. PTEN (phosphatase and tensin homolog) inhibits the class I phosphoinositide 3-kinase (PI3K)-AKT-MTORC1 pathway, promoting autophagy by inhibiting AKT-MTORC1 phosphorylation [63]. SIRT1 (sirtuin 1), and other sirtuins (NAD⁺-dependent class II histone deacetylases), promote autophagy by deacetylating ATG5, ATG7, and mammalian Atg8-family homologs (ATG8s) [64].

Figure 2 depicts the process of autophagy and the pathways by which it is regulated.

Autophagy in kidney disease

Autophagy in RCC

The dual role of autophagy in cancer is widely acknowledged and has significant implications for understanding tumor biology. As RCC progresses, the switch between different isoforms of hypoxia-inducible factors/HIFs and changes in metabolism work together to define autophagy’s dual role [65–68]. In early-stage RCC, mild hypoxic conditions enable the autophagy system to maintain cellular balance by efficiently clearing damaged organelles, especially dysfunctional mitochondria. This process also prevents oxidative stress-induced genomic instability, resulting in significant tumor-suppressive effects [69]. During this phase, HIF1A/HIF-1α, which remains stably expressed, enhances tumor-suppressive metabolic reprogramming by activating BNIP3-dependent selective mitophagy, which in turn inhibits glycolysis [70]. As the tumor progresses to late stages, chronic hypoxia causes a gradual transition from HIF1A to EPAS1/HIF-2α dominance. This shift fundamentally alters the metabolic network, promoting aggressive tumor growth [71]. At this stage, autophagy transforms functionally. It both supports tumor energy by recycling nutrients like glutamine and suppresses anti-tumor immune responses by increasing immune checkpoint molecules such as CD274/PD-L1 [72,73]. In advanced RCC, the upregulation of ITPR1 expression facilitates tumor immune evasion by inducing protective autophagy, which particularly enables resistance to natural killer cell-mediated cytotoxicity [74,75]. Under persistent hypoxia-inducible factor activation, impaired autophagic flux causes abnormal accumulation of SQSTM1/p62. This accumulation constitutively activates the NFE2L2/NRF2 signaling pathway. This significantly enhances the tumor’s antioxidant defense capacity and directly contributes to clinical chemoresistance [69,76].

Autophagy in AKI

AKI is characterized by the rapid loss of kidney function due to ischemic or nephrotoxic damage. Ischemia-reperfusion injury (IRI), sepsis, and nephrotoxic drugs, such as cisplatin, induce intracellular stress in RTECs. This includes hypoxia, ER stress, and oxidative stress, which trigger autophagy. Autophagy generally mediates the clearance of protein aggregates and damaged organelles to maintain cellular homeostasis and prevent renal cell damage [50,51].

IRI, an inflammatory process triggered by the temporary reduction or cessation of organ blood flow and the subsequent restoration of blood flow, is a common cause of AKI. Elevated expression of autophagy-related proteins, such as BECN1 and LC3, and increased autophagosome formation have been observed in rat and mouse renal IRI models [77,78]. The kidneys are more sensitive to renal IRI than wild-type mice in proximal tubules with selective atg5 or atg7 deletion, exhibiting more significant renal dysfunction and tubular cell apoptosis [52]. Similar phenomena have been observed in mice deficient in Pink1 (PTEN induced putative kinase 1) or Prkn (parkin RBR E3 ubiquitin protein ligase) and in pink1 prkn double-knockout mice, which are susceptible to ischemic AKI because the PINK1- and PRKN-dependent mitophagy is inhibited [79]. Moreover, autophagy inhibitors, such as chloroquine and 3-MA, can exacerbate renal IRI and worsen renal tubular apoptosis [80,81].

Sepsis, which is characterized by systemic inflammation, is another common cause of AKI. Lipopolysaccharide (LPS), the most common sepsis-associated AKI (SA-AKI) drug, can induce autophagy in RTECs both in vitro and in vivo [82,83]. Similar to ischemic AKI, increased expression of autophagy-related proteins and increased autophagosome formation have also been observed in AKI caused by LPS-induced sepsis [84]. Moreover, conditional atg7 knockout in renal proximal tubule (atg7-ptKO) mice were more susceptible to LPS-induced AKI than wild-type mice [82,83]. Chloroquine inhibits autophagy and exacerbates LPS-induced AKI [83]. Chloroquine increases kidney damage in mice that also present with the cecal ligation and puncture model of polymicrobial sepsis [85]. However, rapamycin induces autophagy and improves renal function in a cecal ligation and puncture mouse model [86].

Nephrotoxic drugs such as cisplatin are also common causes of AKI. Increased autophagosome formation has been observed in cisplatin-induced AKI [87]. Conditional atg5 knockout in renal proximal tubule (atg5-ptKO) mice resulted in increased sensitivity to cisplatin nephrotoxicity, along with more severe cell apoptosis, ROS production, and DNA damage [50,53]. In addition, cisplatin-induced apoptosis in renal tubular cells increased after the administration of the autophagy inhibitor 3-MA [87].

Autophagy in chronic kidney disease

Chronic kidney disease (CKD) is characterized by progressive loss of renal function and the development of renal fibrosis. It is a highly prevalent irreversible and progressive disease [88,89]. In CKD subtypes, such as diabetic kidney disease (DKD), obstructive nephropathy, and autosomal dominant polycystic kidney disease (ADPKD), autophagy may be induced to protect RTECs and podocytes, whereas impaired autophagy causes progressive CKD [90–93].

DKD is a serious complication of diabetes and a major cause of CKD and end-stage renal disease [94]. In DKD, chronic hyperglycemia and the associated advanced glycation end products lead to dysregulated autophagy in podocytes and TECs, consequently promoting DKD progression. Podocyte-specific atg5 knockout mice exhibited more pronounced mesangial expansion and glomerulosclerosis following streptozotocin (STZ)-induced DKD than wild-type mice [48]. In addition, proximal TECs exposed to high glucose (HG) and tubules from diabetic mice showed increased expression of inositol oxygenase, mitochondrial fragmentation, and decreased autophagy. The inhibition of inositol oxygenase can reactivate mitochondrial autophagy and improve its integrity [49].

Unilateral ureteral obstruction (UUO) is the most common animal model of renal fibrosis. Autophagy also prevents renal fibrosis in UUO-induced CKD models. For instance, atg5-ptKO promotes cell cycle arrest in the G2/M phase and exacerbates renal tubulointerstitial fibrosis after UUO in mice [56]. Furthermore, the conditional knockout of Atg7 in distal RTECs exacerbates renal tubulointerstitial fibrosis and epithelial-stromal transition-like phenotypic changes in UUO mice [95]. However, some studies have reported contradictory findings. For example, the reduction of renal fibrosis has been reported in UUO mice treated with chloroquine to inhibit autophagy or selective knockout of Atg7 in the proximal tubules [57].

ADPKD, which is caused by PKD1 or PKD2 mutations, is a common inherited human disease that can lead to renal failure. In the ADPKD mouse model, elevated expression of autophagy-related proteins and increased autophagosome formation were observed in cystic renal tubular cells [96]. Furthermore, rapamycin inhibited cyst expansion in an ADPKD mouse model [97]. In the ADPKD zebrafish model, atg5-KO inhibits autophagy to promote cyst formation, whereas the use of BECN1 peptide can activate autophagy to improve cyst formation [98].

Regulation of autophagy in RCC by ncRNAs

Autophagy is a double-edged sword in cancer. It acts as both a tumor suppressor to prevent tumorigenesis and as a pro-survival factor that enables cancer cells to survive metabolic stress and chemotherapeutic agents. Aberrant autophagy regulated by ncRNAs is potentially involved in the development of RCC.

Regulation of autophagy in RCC by miRNAs

Inhibition of autophagy in RCC by miRNAs

miRNAs can suppress autophagy in RCC, thereby reducing its pathogenic processes. Most ccRCC cases involve the loss of VHL, which is a tumor suppressor gene. For example, a decrease in MIR204 expression was observed in 128 human ccRCC tissues, contrary to 114 healthy kidney samples. MIR204 binds to the 3' UTR of LC3B, which reduces LC3B expression in VHL(-) RCC cells. During the developmental phase of autophagy, it distinctly suppressed macroautophagy triggered by starvation in VHL(-) RCC cells, as opposed to VHL(+) RCC cells. The inhibition of macroautophagy by exogenous MIR204 causes RCC cells to become synthetically lethal and succumb to necrosis-induced cell death due to starvation [99]. Additionally, VHL directly binds to the 3' UTR of TRPM3/Melastatin 3 (transient receptor potential cation channel subfamily M member 3), hindering its expression via MIR204. Alternatively, it can indirectly suppress TRPM3 by targeting CAV1 (caveolin 1), another target of MIR204. The inhibition of TRPM3 leads to lower intracellular concentrations of calcium, which suppresses ULK1 phosphorylation and autophagy. This ultimately prevents the growth of tumors in orthotopic xenografts [100]. The exogenous expression of MIR30A in 786-O or A489 cells inhibited BECN1 expression and enhanced sorafenib-induced cytotoxicity, resulting in the apoptosis of numerous RCC cells [101]. Additionally, HMOX1/HO-1 (heme oxygenase 1), an anti-apoptotic gene, plays a role in regulating autophagy in cancer [102]. MIR200C targets HMOX1 to induce apoptosis and autophagy, suppressing ccRCC proliferation and improving drug sensitivity to sorafenib/imatinib [103].

Promotion of autophagy in RCC by miRNAs

Conversely, miRNAs may enhance RCC progression by promoting autophagy. MIR501-5p exhibited increased expression in KJ29, Caki-1, and Caki-2 renal cancer cell lines compared to that in normal epithelial kidney 4/5 and human embryonic kidney cell line 293 (HEK293) cells. MIR501-5p binds to the 3' UTR of MCU (mitochondrial calcium uniporter) mRNA, leading to a decreased production of MCU protein. Mitochondrial Ca²⁺ levels were notably diminished after ATP stimulation. This triggers AMPK, leading to the initiation of autophagy independent of MTOR. Additionally, this triggers the breakdown of the tumor-inhibiting protein TP53. This further emphasizes the complex functions of ncRNAs in the regulation of autophagy during RCC progression [104].

Regulation of autophagy in RCC by lncRNAs

Inhibition of autophagy in RCC by lncRNAs

lncRNA HOTTIP enhances the phosphorylation of PI3K and AKT while simultaneously diminishing ATG13 expression in RCC patient tissues. This results in the suppression of autophagy, thereby promoting the growth, migration, and penetration of RCC cells [105]. Moreover, lncRNA LBX2-AS1 promotes the proliferation and migration of ccRCC by inhibiting mitophagy [106].

Promotion of autophagy in RCC by lncRNAs

In addition to inhibiting autophagy, lncRNAs enhance RCC progression by promoting autophagy. lncRNA IGFL2-AS1 increases tumor protein TP53INP2 (tumor protein p53 inducible nuclear protein 2) mRNA levels in sunitinib-resistant RCC cells by competitively binding to HNRNPC (heterogeneous nuclear ribonucleoprotein C). This protein post-transcriptionally reduces TP53INP2 expression through alternative splicing. The upregulation of TP53INP2 expression leads to increased autophagy, thereby conferring sunitinib resistance in RCC cells [107].

Regulation of autophagy in RCC by ceRNA-miRNA axes

The regulatory network involving ceRNAs, such as lncRNAs and circRNAs, depends on their ability to act like sponges that bind to and inhibit miRNAs. Such interactions are pivotal in modulating various cellular processes and biological functions.

Inhibition of autophagy in RCC by ceRNA-lncRNA axes

lncRNA SBF2-AS1 acts as a ceRNA that targets MIR338-3p, upregulating the expression of ETS1 (ETS proto-oncogene 1, transcription factor). This suppresses ccRCC cell death and autophagy, consequently facilitating their proliferation, migration, and infiltration [108].

Promotion of autophagy in RCC by ceRNA-miRNA axes

Increased levels of lncRNA KIF9-AS1 in RCC cells promote cell survival and reduce cell death during sorafenib treatment. This phenomenon results from increased ATG9A activity and decreased SQSTM1/p62 levels. The diminished SQSTM1/p62 levels are attributed to the targeting of MIR497-5p by lncRNA KIF9-AS1, which facilitates RCC drug resistance through chemical processes [109]. Additionally, circRNA microarray analysis revealed increased circ0054537 levels in RCC tissues [110]. Furthermore, circ0054537 was identified as a ceRNA for MIR640, which binds to the 3' UTR of NPTX2 (neuronal pentraxin 2) mRNA. Eliminating circ0054537 in vitro effectively disrupts cellular movement, penetration, autophagy, and glycolysis and slows tumor development in living organisms [111]. Moreover, extensive sequencing revealed higher expression levels of circ0035483 in RCC. An inverse relationship was observed between this circRNA and MIR335. circ0035483 binds to MIR335 in sorafenib-treated RCC cells, enabling its targeting of the 3' UTR of CCNB1 (cyclin B1) mRNA. Thus, suppression of CCNB1 expression triggers autophagy, curbs apoptosis, and increases sorafenib resistance. These processes have a notable effect on the results of chemotherapy in RCC [112].

The autophagy-regulated ncRNAs and their targets in RCC are concluded in Figure 3 and Table 1.

Table 1.

Non-coding RNAs regulate autophagy in renal cell Carcinoma (RCC).

ncRNAs	Expression in RCC/non-RCC tissue	Animal/human (numbers of clinical samples)	Cell line	Potential target (Direct or Indirect*)	Gain- or loss- of- function studies	Autophagy modulation	Influence on RCC pathogenesis	Ref.
MIR148	Down	Human	Human RCC cell lines (A498, 786-O)	ADAMTS18 (Indirect)	+/+	Inhibition	Suppression (Proliferation↓)	[113]
MIR200C	Down	Human	Human RCC cell lines (SN12C, ACHN, 786-O, Caki-1)	HMOX1 (Direct)	+/+	Inhibition	Suppression (Proliferation↓, Drug resistance↓, Apoptosis↑)	[103]
MIR204	Down	Mouse and human; 128 human RCC with VHL status and 114 cases matched normal kidney specimen	Human RCC cell lines (786-O, A498, Caki-1)	LC3B (Direct)	+/+	Inhibition	Suppression (Necrotic cell death↑)	[99]
MIR204	Down	Mouse and human; 66 human RCC tumors with VHL-inactive and 24 human RCC tumors with wild type VHL	Human RCC cell lines (786-O, A498, Caki-1)	TRPM3 (Direct), CAV1 (Direct)	+/+	Inhibition	Suppression (Proliferation↓)	[100]
MIR30A	Down	Human; 10 fresh human RCC tissues of different-grades (AJCC stages 1–4) and surrounding normal tissues	Human RCC cell lines (786-O, A498, SK-RC-44)	BECN1 (Indirect)	+/+	Inhibition	Suppression (Drug resistance↓)	[101]
MIR501-5p	Up	Human	Non papillary kidney cancer KJ29 cells; RCC cell lines (Caki-1)	MCU (Direct)	+/+	Promotion	Enhancement (Proliferation↑, Migration↑)	[104]
lncRNA HOTTIP	Up	Mouse and human; 42 paired human RCC and adjacent normal samples	Human RCC cell lines (786-O, A498, ACHN, OSRC-2)	PI3K-AKT-ATG13 (Indirect)	+/+	Inhibition	Enhancement (Proliferation↑, Migration↑, Invasion↑)	[105]
lncRNA IGFL2-AS1	Up	Human; 72 patients with RCC and all patients underwent nephrectomy before sunitinib therapy	Human RCC cell lines (786-O, 769-P, ACHN)	HNRNPC (Direct)	+/+	Promotion	Enhancement (Drug resistance↑)	[107]
lncRNA KIF9-AS1	–	Human	Human RCC cell lines (Caki, 786-O)	MIR497-5p (Direct)	+/+	Promotion	Enhancement (Drug resistance↑)	[109]
LncRNA LBX2-AS1	Up	Mouse and human; 96 paired RCC tissues and adjacent non-tumor tissues	Human RCC cell lines (769-P, Caki-1)	FOXO3 (Indirect)	-/+	Inhibition	Enhancement (Proliferation↑, Migration↑)	[106]
lncRNA SBF2-AS1	Up	Mouse and human; cancer tissues or adjacent tissues from 46 patients with RCC	Human RCC cell lines (Caki-1, UT14, UT16, UT33a, 786-O); Human renal proximal tubular cell lines (HK-2)	MIR338-3p (Direct)	+/+	Inhibition	Enhancement (Proliferation↑, Migration↑, Invasion↑, Apoptosis↓)	[108]
circ0035483	Up	Human; 3 kidney cancer specimens and 3 paired contra lateral normal specimens	Human RCC cell lines (TK10, UO31)	MIR335 (Direct)	+/+	promotion	Enhancement (Drug resistance↑)	[112]
circ0054537	Up	Mouse and human; RCC specimens were surgically obtained from 39 patients diagnosed with RCC	Human RCC cell lines (786-O, A498); Human renal proximal tubular cell lines (HK-2)	MIR640 (Direct)	+/+	promotion	Enhancement (Proliferation↑, Migration↑, Invasion↑, Apoptosis↓)	[111]

Open in a new tab

*Direct: interactions validated by luciferase reporter assays, RNA immunoprecipitation assays, or RNA affinity-isolation assays. Indirect: expression correlations only.

Regulation of autophagy in AKI by ncRNAs

Autophagy generally plays a protective role in AKI, despite some exceptions. ncRNAs-regulated autophagy dysfunction is potentially linked to AKI advancement.

Regulation of autophagy in AKI by miRNAs

Inhibition of autophagy in AKI by miRNAs

miRNAs can promote the progression of AKI by inhibiting autophagy. For example, MIR21 regulates RAB11A expression at the post-transcriptional level without affecting its mRNA level but inhibits its protein level in rat kidneys subjected to I/R or I/R-treated NRK-52E cells. This suppression results in inhibited autophagy in I/R-induced AKI in rat kidneys, reduced cell viability in NRK-52E cells, and increased cell apoptosis [114]. Furthermore, MIR20A-5p suppresses autophagy by downregulating ATG16L1 expression, a factor crucial for cell survival during ischemic kidney injury [115]. In addition, MIR30B can further aggravate apoptosis and inflammation, as well as impair autophagy in LPS-induced HK2 cells. This is achieved by loading this miRNA into ion-crosslinked polysaccharide nanoparticles [116]. Moreover, MIR34A binds to the 3' UTR of ATG4B, leading to a post-transcriptional suppression of ATG4B expression. This consequently hinders autophagic activity in I/R-treated RTECs and results in cellular damage [117]. Furthermore, MIR30E-5p inhibits autophagy by diminishing the expression of BECN1 and fostered CASP3 (caspase 3) production, which triggers apoptosis in HK2 cells subjected to urografin exposure [118].

miRNAs may also alleviate AKI progression by inhibiting autophagy. An increase in LC3-II/I and BAX levels, along with a reduction in BCL2 expression, was observed in NRK-52E cells challenged with iodixanol. Increasing MIR1-3p levels may inhibit autophagy and subsequent apoptosis in NRK-52E cells by targeting ATG13 and activating the AKT signaling pathway. This action helps mitigate kidney damage in rats with contrast-induced AKI [119]. Moreover, MIR526B can bind to the 3' UTR within ATG7 mRNA in both AKI mouse kidney tissues and LPS-activated HK2 cells. This leads to decreased post-transcriptional expression and inhibits autophagy, consequently mitigating SA-AKI damage caused by excessive autophagy [120]. MIR92A suppresses MAP2K4/MEK4-MAPK8/JNK1-related autophagy, mitigating kidney IRI [121].

Promotion of autophagy in AKI by miRNAs

miRNAs can delay AKI progression by promoting autophagy. For instance, MIR590-3p binds to the 3' UTR of TRAF6 (TNF receptor associated factor 6) mRNA, which suppresses TRAF6 expression. This leads to increased expression of LC3-I and BECN1, decreased SQSTM1/p62 expression, enhanced autophagy, and improved defense against kidney I/R damage [122]. Additionally, MIR506-3p may inhibit PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) expression by binding to the 3' UTR of PIK3CA mRNA. Furthermore, it may promote autophagy to reverse renal tissue damage, mitochondrial structural alterations, and cell demise in mouse RTECs affected by SA-AKI [123]. MIR365-3p targets Rheb (ras homolog enriched in brain), promoting autophagy in RTECs and reducing apoptosis induced by contrast media [124]. Moreover, MIR145 from human umbilical cord-derived mesenchymal stem cells promotes autophagy in HK-2 cells by inhibiting the PI3K-AKT-MTOR signaling pathway [125].

Regulation of autophagy in AKI by lncRNAs

Like miRNAs, lncRNAs can worsen AKI by inhibiting autophagy. The lncRNA EGOT specifically decreases the expression of ATG7 and ATG16L1, thereby hindering the development of autophagosomes in H/R-treated HK2 cells [126].

Regulation of autophagy in AKI by circRNAs

Despite limited research, circRNAs play a significant role in regulating autophagy and the progression of AKI. Aberrant expression of circRNAs significantly impacts AKI by regulating autophagy. Contrary to typical circRNAs that act as miRNA sponges, circZNF609 was highly expressed in the urine of 119 AKI patients and in the renal tissue of rats following I/R treatment. In addition, this circRNA produces a functioning protein with 250 amino acids (aa), designated as ZNF609-250aa. ZNF609-250aa triggers the AKT3-MTOR signaling pathway, disrupting autophagy in HK2 cells, which promotes apoptosis and hinders proliferation [127].

Regulation of autophagy in AKI by the ceRNA-miRNA axes

Inhibition of autophagy in AKI by the ceRNA-miRNA axes

lncRNA SNHG14 decreases the levels of MIR495-3p and increases the expression of HIPK1 (homeodomain interacting protein kinase 1). This leads to increased expression of BAX, cleaved CASP3 (caspase 3), and SQSTM1/p62. In contrast, lncRNA SNHG14 decreases the expression of BCL2 and LC3-II in LPS-treated HK2 cells [128].

Promotion of autophagy in AKI by the ceRNA-miRNA axes

As a ceRNA, lncRNA HCG18 binds to MIR16-5p, promoting BCL2 expression, which facilitates cellular autophagy and suppresses apoptosis in IRI-induced AKI [129]. The ceRNA-miRNA axis may promote AKI progression by enhancing autophagy. lncRNA TUG1, a ceRNA, interacts with MIR29A to enhance the expression of its target gene PTEN. This process promotes autophagy and fosters apoptosis and inflammation of kidney tubular cells after H/R treatment [130]. Moreover, lncRNA NKILA enhances CLDN2 (claudin 2) expression by acting as a ceRNA for MIR140-5p, which promotes autophagy, apoptosis, and inflammatory responses in LPS-treated HK2 cells [131]. Furthermore, the lncRNA MEG3-MIR145-5p-RTKN-WNT-CTTNB1/β-catenin-MYC/c-MYC positive feedback loop aggravates renal IRI by activating mitophagy and apoptosis [132].

The autophagy-related ncRNAs involved in AKI, along with their targets, are provided in Figure 4 and Table 2.

Table 2.

Non-coding RNAs regulate autophagy in acute kidney injury (AKI).

ncRNAs	Expression in AKI/non-AKI tissue	Animal/human (numbers of clinical samples)	Cell line	Potential target (Direct or Indirect*)	Gain- or loss- of- function studies	Autophagy modulation	Influence on AKI pathogenesis	Model/Treatment	Ref.
MIR1-3p	Up	Rat	Rat renal proximal tubular epithelial cell line (NRK-52E)	ATG13 (Direct)	+/+	Inhibition	Suppression (Apoptosis↓, Fibrosis↓)	Animal: Iodixanol; Cell: Iodixanol	[119]
MIR145	–	Human	Human renal proximal tubular cell line (HK-2)	PI3K-AKT-MTOR (Indirect)	+/+	Promotion	Suppression	Animal: -; Cell: AOPP	[125]
MIR20-5p	Down	Mouse and human	Human renal proximal tubular cell line (HK-2)	ATG16L1 (Direct)	+/+	Inhibition	Enhancement	Animal: I/R; Cell: H/R	[115]
MIR21	Up	Rat	Rat renal proximal tubular epithelial cell line (NRK-52E)	RAB11A (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: I/R; Cell: H/R	[114]
MIR30B	Up	Human	Human renal proximal tubular cell line (HK-2)	–	+/+	Inhibition	Enhancement (Apoptosis↑, Inflammation↑)	Animal: -; Cell: LPS	[116]
MIR30E-5p	Up	Human	Human renal proximal tubular cell line (HK-2)	BECN1 (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: -; Cell: Urografin	[118]
MIR34A	Up	Mouse	Primary mouse proximal tubular epithelial cells	ATG4B (Direct)	+/+	Inhibition	Enhancement	Animal: I/R; Cell: -	[117]
MIR506-3p	–	Mouse	Mouse renal tubular epithelial cells	PIK3CA (Direct)	+/+	Promotion	Suppression (Apoptosis↓)	Animal: LPS; Cell: LPS	[123]
MIR526B	Down	Mouse and human	Human renal proximal tubular cell line (HK-2)	ATG7 (Direct)	+/+	Inhibition	Suppression (Cell viability↑)	Animal: CLP; Cell: LPS	[120]
MIR590-3p	Up	Human; 25 patients consisted of 12 young and 13 elderly AKI patients	Human renal proximal tubular cell line (HK-2)	TRAF6 (Direct)	+/+	Promotion	Suppression	Animal: -; Cell: H/R	[122]
MIR92A	Down	Mouse and human	Human renal proximal tubular cell line (HK-2)	MEK4 (Direct)	+/+	Inhibition	Suppression (Apoptosis↓)	Animal: I/R; Cell: H/R	[121]
lncRNA EGOT	Down	Human	Human renal proximal tubular cell line (HK-2)	ELAVL1/HuR (Direct)	+/+	Inhibition	Enhancement	Animal: -; Cell: H/R	[126]
lncRNA HCG18	Down	Mouse and human	Human renal proximal tubular cell line (HK-2)	MIR16-5p (Direct)	+/+	Promotion	Suppression (Apoptosis↓, Inflammation↓)	Animal: I/R; Cell: H/R	[129]
lncRNA MEG3	Up	Mouse and human	Human renal proximal tubular cell line (HK-2)	MIR145-5p (Direct)	-/+	Promotion	Enhancement (Apoptosis↑)	Animal: I/R; Cell: H/R	[132]
lncRNA NKILA	Up	Human	Human renal proximal tubular cell line (HK-2)	MIR140-5p (Direct)	-/+	Promotion	Enhancement (Apoptosis↑, Inflammation↑)	Animal: - Cell: LPS	[131]
lncRNA SNHG14	Up	Human; 20 blood samples from patients with sepsis-induced AKI or healthy controls	Human renal proximal tubular cell line (HK-2)	MIR495-3p (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑, Inflammation↑)	Animal: -; Cell: LPS	[128]
lncRNA TUG1	Up	Rat and human	Human renal proximal tubular cell line (HK-2)	MIR29A (Direct)	±	Promotion	Enhancement (Apoptosis↑, Inflammation↑)	Animal: I/R; Cell: H/R	[130]
circZNF609	Up	Rat and human; 119 urine samples from patients with acute heart failure	Human renal proximal tubular cell line (HK-2)	AKT3-MTOR (Indirect)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: I/R; Cell: H/R	[127]

Open in a new tab

*Direct: interactions validated by luciferase reporter assays, RNA immunoprecipitation assays, or RNA affinity-isolation assays. Indirect: expression correlations only.

Regulation of autophagy in CKD by ncRNAs

Similar to AKI, autophagy is frequently regarded as a protective mechanism in CKD. The progression of CKD may include abnormal autophagy mediated by ncRNAs.

Regulation of autophagy in CKD by miRNAs

Inhibition of autophagy in CKD by miRNAs

MIR214 suppressed autophagy by inhibiting ULK1 expression, which aggravated kidney enlargement and albuminuria in diabetic kidney cells and tissues [133]. Similarly, MIR22 inhibited autophagy by binding to PTEN mRNA; reducing the expression of LC3-II/I; and increasing the expression of COL4A (collagen type IV alpha), ACTA2 (actin alpha 2, smooth muscle) and SQSTM1/p62 [134]. Additionally, MIR543 suppresses autophagy and promotes fibrosis by reducing TSPAN8 (tetraspanin 8) expression in HG-induced HK2 cells [135]. Furthermore, MIR379 binds to FIS1 (fission, mitochondrial 1) mRNA to inhibit mitophagy. This results in the accumulation of the extracellular matrix, fibrosis, damage to and loss of podocytes, thickening of the glomerular basement membrane, and enlargement of glomeruli in DKD mice [136]. Additionally, MIR122-5p prevented autophagy and elevated TGFB1 (transforming growth factor beta 1), COL1A (collagen type I alpha), COL3A (collagen type III alpha), FN1 (fibronectin 1), IL6 (interleukin 6), and IL18 (interleukin 18) expression. It further improved the rate of TUNEL-positive staining in spontaneous hypertensive rat kidneys by reducing FOXO3 (forkhead box O3) expression [137]. MIR376B inhibits ATG5 expression and promotes collagen buildup and interstitial fibrosis in the kidneys of mice with CKD induced by adenine gavage and a phosphate-rich diet [138]. MIR34A inhibits ATG4B expression, elevating ROS levels and inflammation in human renal glomerular endothelial cells induced by HG [139].

Promotion of autophagy in CKD by miRNAs

Exosomal MIR125B from mesenchymal stem cells boosts autophagy and prevents cell death by binding to the 3' UTR of TRAF6 mRNA, thus lowering its expression in HG-treated HKCs [140]. The exosomal MIR25-3p, originating from M2 macrophages, suppresses DUSP1 (dual specificity phosphatase 1) expression by binding the 3' UTR of its mRNA, consequently fostering autophagy in podocytes and mitigating the damage caused by HG levels [141]. Similarly, MIR29A bound to the 3' UTR sequence of HMOX1 mRNA triggers autophagy and reduces cell death in HG-induced podocytes [142]. Furthermore, MIR4516 improves mitochondrial autophagy and boosts mitochondrial activity by suppressing SIAH3 (siah E3 ubiquitin protein ligase family member 3), an E3 ubiquitin ligase that reduces PINK1 buildup in impaired mitochondria. This ameliorated renal cell death and fibrosis in mice [143].

Regulation of autophagy in CKD by lncRNAs

Inhibition of autophagy in CKD by lncRNAs

Aberrant expression of lncRNAs enhances CKD progression by inhibiting autophagy. SIRT1 triggers autophagy through the deacetylation of autophagy-associated genes, such as BECN1. lncRNA RISA suppresses SIRT1 phosphorylation at Ser27 in mice with DKD and those receiving HG treatment of mesangial progenitor cells, thereby diminishing its functionality and expression. This reduces GSK3B (glycogen synthase kinase 3 beta) phosphorylation at Ser9, consequently worsening autophagy, podocyte impairment, proteinuria, and glomerular damage in DKD mice [144]. lncRNA H19 aggravates puromycin-induced podocyte damage by inhibiting lncRNA H19-DIRAS3 (DIRA family GTPase 3)-mediated autophagy [145]. In addition to nonselective autophagy, lncRNAs mediate disease progression by regulating selective autophagy in DKD. For example, lncRNA SNHG17 impairs PRKN-dependent mitophagy by inhibiting STK4/MST1 (serine/threonine kinase 4) degradation, thereby promoting podocyte apoptosis [146]. In addition, lncRNA LINC279227 silencing improved downregulation of the expression of mitophagy-related proteins PINK1 and PRKN. However, it decreased the expression of phosphorylated dynamin-related protein and increased the expression of MFN2 (mitofusin 2), which ameliorates the inhibition of mitophagy in HG-treated RTEC and alleviates mitochondrial fusion/fission perturbation [147].

Promotion of autophagy in CKD by lncRNAs

lncRNA HOXB3OS enhances autophagy in HG-exposed MPC5 cells by disrupting the AKT-MTOR signaling pathway, possibly due to an increase in SIRT1 expression levels [148]. lncRNA AA465934 binds to ZFP36/TTP (ZFP36 ring finger protein), which inhibits the TTP-PIM2 (Pim-2 proto-oncogene, serine/threonine kinase) interaction. This action reduces HMGB1 (high mobility group box 1) levels, reverses the downregulation of autophagy, and alleviates podocyte injury and diabetic nephropathy caused by HG [149].

Regulation of autophagy in CKD by ceRNA-miRNA axes

Inhibition of autophagy in CKD by ceRNA-miRNA axes

lncRNA SPAG5-AS1 suppresses autophagy through two complementary mechanisms by stabilizing SPAG5 mRNA through MIR789-5p sequestration, while simultaneously inhibiting USP14-mediated SPAG5 protein degradation. Consequently, this dual action activates the AKT-MTOR pathway, ultimately exacerbating podocyte apoptosis [147].

Promotion of autophagy in CKD by ceRNA-miRNA axes

lncRNA XIST (X inactive specific transcript) targets MIR30D-5p, regulates BECN1 expression, ameliorates HG-induced autophagy decline in MPC5 cells, and inhibits cell apoptosis [150]. Similarly, lncRNA SOX2-OT acts as a ceRNA that promotes SIRT1 expression by sponging MIR9. This process induces autophagy and alleviates HPC damage caused by HG [151]. circRNAs are recently gaining attention for their role in autophagy regulation during the progression of CKD. As revealed by transcriptome sequencing, decrease in circ0000953 expression was found in podocytes from STZ-induced diabetic mice. Also, the deficiency of a homologous sequence of circ0000953 was found in kidney biopsy samples from DKD patients. circ0000953 directly binds to MIR665-3p to regulate autophagy process in an ATG4B-dependent manner, suggesting it could be a potential therapeutic target for prevention and treating DKD [152].

The autophagy-related ncRNAs involved in CKD and their targets are provided in Figure 5 and Table 3.

Table 3.

Non-coding RNAs regulate autophagy in chronic kidney disease (CKD).

ncRNAs	Expression in CKD/non-CKD tissue	Animal/human (numbers of clinical samples)	Cell line	Potential target (Direct or Indirect*)	Gain- or loss- of- function studies	Autophagy modulation	Influence on CKD pathogenesis	Model/Treatment	Ref.
MIR122-5p	Up	Rat and mouse	Primary mouse renal tubular interstitial fibroblasts	FOXO3 (Indirect)	+/+	Inhibition	Enhancement (Fibrosis↑, Apoptosis↑)	Animal: Spontaneously hypertensive rats; Cell: Ang II	[137]
MIR125B	Down	Mouse and human; 15 pairs of DKD tissues and adjacent normal tissues	Human embryonic kidney epithelial cells	TRAF6 (Direct)	+/+	Promotion	Suppression (Apoptosis↓)	Animal: -; Cell: HG	[140]
MIR155-5p	Up	Rat and human	Rat renal proximal tubular epithelial cell line (NRK-52E)	PTEN (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑)	Animal: -; Cell: HG	[153]
MIR21	Up	Mouse and human	Primary human podocytes	FOXO1 (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: KK Ay mice; Cell: HG	[154]
MIR214	Up	Mouse and human; renal biopsies from 20 diabetic patients and 14 non diabetic patients	Renal proximal tubular cell lines (RPTC, BUMPT)	ULK1 (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑)	Animal: Akita mice, STZ; Cell: HG	[133]
MIR22	Up	Rat	Rat renal proximal tubular epithelial cell line (NRK-52E)	PTEN (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑)	Animal: STZ; Cell: HG	[134]
MIR25-3p	Down	Mouse	Mouse podocytes	DUSP1 (Direct)	-/+	Promotion	Suppression (Fibrosis↓, Apoptosis↓)	Animal: -; Cell: HG	[141]
MIR29A	Down	Mouse	Mouse podocytes	HMOX1 (Direct)	±	Promotion	Suppression (Apoptosis↓)	Animal: -; Cell: HG	[142]
MIR34A	Up	Mouse and human; DKD patient and MCD patient tissues	Human podocytes	SIRT1 (Indirect)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: STZ; Cell: AGEs	[155]
MIR376B	Up	Mouse	Primary mouse kidney fibroblasts	ATG5 (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑, Apoptosis↑)	Animal: High-Phosphate Diet Model;Cell: -	[138]
MIR379	Up	Mouse	Primary mouse mesangial cells	FIS1 (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑)	Animal: STZ; Cell: HG	[136]
MIR4516	Down	Mouse and human	Human proximal tubular epithelial cells (TH1)	SIAH3 (Indirect)	-/+	Promotion	Suppression (Fibrosis↓)	Animal: Adenine Diet Model; Cell: p-Cresol	[143]
MIR543	Down	Mouse and human	Human renal proximal tubular cell line (HK-2)	TSPAN8 (Direct)	+/+	Inhibition	Enhancement (Fibrosis↑)	Animal: db/db; Cell: HG	[135]
lncRNA AA465934	Down	Mouse	Mouse podocytes cell line (MPC5)	TTP (Direct)	±	Promotion	Suppression (Apoptosis↓)	Animal: db/db; Cell: HG	[149]
lncRNA H19	Up	Rat	Primary rat podocytes	DIRAS3 (Indirect)	-/+	Inhibition	Enhancement (Podocytes injury↑)	Animal: Puromycin; Cell: Puromycin	[145]
lncRNA HOXB3OS	Down	Mouse	Mouse podocytes cell line (MPC5)	SIRT1 (Indirect)	±	Promotion	Suppression (Apoptosis↓)	Animal: db/db; Cell: HG	[148]
lncRNA GM15645	Down	Mouse	Primary mouse podocytes	–	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: db/db Cell: HG	[156]
lncRNA GM5524	Up	Mouse	Primary mouse podocytes	–	+/+	Promotion	Suppression (Apoptosis↓)	Animal: db/db; Cell: HG	[156]
lncRNA LINC279227	Up	Mouse	Mouse renal tubular epithelial cells	–	-/+	Inhibition	Enhancement (mitochondrial dysfunction↑)	Animal: db/db; Cell: HG	[147]
lncRNA RISA	Up	Mouse	Mouse podocytes cell line (MPC5)	SIRT1 (Indirect)	+/+	Inhibition	Enhancement (Podocytes injury↑)	Animal: db/db; Cell: HG	[144]
lncRNA SNHG17	Up	Mouse	Mouse podocytes cell line (MPC5)	MST1 (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: STZ; Cell: HG	[146]
lncRNA SOX2-OT	Down	Human	Human podocytes	MIR9 (Direct)	+/+	Promotion	Suppression (Apoptosis↓)	Animal: -; Cell: HG	[151]
lncRNA SOX2-OT	Down	Mouse	Mouse mesangial cells	AKT-MTOR (Indirect)	±	Promotion	Suppression (Fibrosis↓)	Animal: STZ; Cell: HG	[157]
lncRNA SPAG5-AS1	Up	Human	Human podocytes	MIR769-5p (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: -; Cell: HG	[158]
lncRNA XIST	Down	Mouse	Mouse podocytes cell line (MPC5)	MIR30D-5p (Direct)	±	Promotion	Suppression (Fibrosis↓, Apoptosis↓)	Animal: STZ; Cell: HG	[150]
circ0000953	Down	Mouse and human; renal biopsies from 8 T1D patients and 13 T2D patients	Mouse podocytes cell line (MPC5)	MIR665-3p (Direct)	+/+	Promotion	Suppression (Podocytes injury↓, Inflammation↓)	Animal: STZ; Cell: HG	[152]

Open in a new tab

*Direct: interactions validated by luciferase reporter assays, RNA immunoprecipitation assays, or RNA affinity-isolation assays. Indirect: expression correlations only.

ncRNAs regulate autophagy in other kidney diseases

Kidney stone

The serum and renal tissue mRNA levels in 20 patients with kidney stones revealed significantly increased MIR155 expression. Similarly, MIR155 expression was upregulated in a renal tubular cell model of kidney stones constructed using CaOx crystal treatment. Upregulation of MIR155 expression activates autophagy and promotes cell damage by inhibiting the expression of its downstream target, PIK3CA. This subsequently inhibits the PI3K-AKT-MTOR signaling pathway. Contrastingly, MIR155 silencing or treatment with the autophagy inhibitor 3-MA ameliorated the cellular damage induced by CaOx crystals [159]. Furthermore, reduced MIR20B-3p expression levels have been observed in the urine of patients with hyperoxaluria and in rat models of ethylene glycol-induced hyperoxaluria. Treatment with MIR20B-3p extracted from fat-derived matrix cells inhibited oxalate-induced cellular autophagy and inflammation by targeting the downstream molecule ATG7 and reducing its expression [160].

IgA nephropathy

In mesangial cell-derived exosomes treated with aIgA1, MIR4455 expression is significantly upregulated and can be transferred by exosomes from mesangial cells to podocytes. Exosomal MIR4455 directly targets ULK2 and downregulates its expression. This suppresses autophagy and induces podocyte injury [161].

Lupus nephritis

lncRNA HOXA11-OS expression was elevated in lupus nephritis tissues, serum, and cells, whereas MIR124-3p expression was decreased. lncRNA HOXA11-OS acts as a competitive endogenous RNA for MIR124-3p to CCN1/CYR61 (cellular communication network factor 1) expression. This consequently enhances lupus nephritis-IgG-induced autophagy and aggravates podocyte injury. However, sh-HOXA11-OS adeno-associated virus significantly attenuated kidney injury in mice with lupus [162].

Focal and segmental glomerulosclerosis (FSGS)

In a rat model of FSGS induced by 5/6 nephrectomy, glomerular expression of autophagy-related proteins (LC3B, BECN1, ATG7, and ATG5) was significantly downregulated, concomitant with glomerular injury. miRNA profiling revealed upregulated levels of MIR34C, MIR132, and MIR214 in the renal tissue of these FSGS rats. Functional studies showed that transfection with MIR34C, MIR132, or MIR214 mimics suppressed key autophagy-related protein expression in podocytes, while their respective antagonists restored it. These results imply that MIR34C, MIR132, and MIR214 promote FSGS progression by impairing autophagy, suggesting their therapeutic targeting as a potential strategy [163].

The autophagy-related ncRNAs involved in other kidney diseases and their targets are provided in Table 4.

Table 4.

Non-coding RNAs regulate autophagy in other kidney diseases.

ncRNAs	Disease	Expression in disease/non-disease tissue	Animal/human (numbers of clinical samples)	Cell line	Potential target (Direct or Indirect*)	Gain- or loss- of- function studies	Autophagy modulation	Influence on disease pathogenesis	Model/Treatment	Ref.
MIR155	Kidney stone	Up	Human; peripheral blood samples from 20 patients with calcium oxalate nephrolithiasis and 20 normal volunteers	Human renal proximal tubular cell line (HK-2)	PIK3CA (Direct), RHEB (Direct)	+/+	Promotion	Enhancement (Apoptosis↑, Inflammation↑)	Animal: -; Cell: CaOx crystal	[159]
MIR20B-3p	Kidney stone	Down	Rat and human; urine samples from 30 kidney stone patients and 30 healthy controls	Rat renal proximal tubular epithelial cell line (NRK-52E)	ATG7 (Direct), TLR4 (Direct)	±	Inhibition	Suppression (Inflammation)↓	Animal: Ethylene glycol; Cell: Oxalate	[160]
MIR4455	IgA nephropathy	Up	Human	Primary human podocytes; human glomerular mesangial cells	ULK2 (Direct)	+/+	Inhibition	Enhancement (Apoptosis↑)	Animal: -; Cell: aIgA1	[161]
MIR214, MIR132, MIR34C	Focal segmental glomerulos-clerosis	Up	Rat	Primary rat podocytes	BECN1, LC3B, ATG7, ATG5 (Indirect)	+/+	Inhibition	Enhancement	Animal: 5/6 nephrectomy models, adriamycin; Cell: -	[163]
lncRNA HOXA11-OS	Lupus nephritis	Up	Mouse and human; Serum of 20 patients with diagnosed LN and 10 healthy people	Mouse podocytes cell line (MPC5)	MIR124-3p (Direct)	+/+	Promotion	Enhancement (Podocytes injury↑)	Animal: MRL/lpr female mice; Cell: Serum IgG from patients with lupus	[162]

Open in a new tab

*Direct: interactions validated by luciferase reporter assays, RNA immunoprecipitation assays, or RNA affinity-isolation assays. Indirect: expression correlations only.

Clinical applications of non-coding RNAs by autophagy regulation in kidney diseases

ncRNAs are crucial in the development of kidney diseases and are increasingly recognized as both diagnostic biomarkers and therapeutic targets, particularly in relation to autophagy regulation. This section systematically discusses diagnostic biomarkers, therapeutic targets, emerging technologies, and existing challenges in the field. In addition, an overview of clinical applications of non-coding RNAs in kidney diseases along with the pros/cons-limitations is provided in Table 5.

Table 5.

Overview of clinical applications of non-coding RNAs.

Applications	ncRNA	Advantages	Limitations	Example in Kidney Diseases [Ref.]
Diagnostics	miRNA	Small size, highly conserved sequences, high detectability; body fluid stability, noninvasive diagnostic compatibility	High sequence homology (difficult differentiation); individual miRNA specificity limitations	Elevated urinary MIR452 enables early detection of sepsis-AKI (AUC = 0.90, sensitivity 87.2%), showing strong correlation with creatinine (r = 0.83) [164]
	lncRNA	Strong tissue-specific expression, potentially higher disease specificity	Complex structures, low stability; low abundance requires high detection sensitivity	Combined detection of conservative lncRNAs (HILPDA and PRND) in blood enable early PC-AKI diagnosis (AUC 0.885/0.875 respectively) with 100% sensitivity and 83.93% specificity [165]
	circRNA	Covalently closed circular structure (exonuclease-resistant, highly stable); enhanced detection sensitivity in fluids	Circularity complicates amplification/sequencing (requires specialized primers/algorithms); underdeveloped databases and standardized assays	circ0072463 (AUC = 0.866) serves as a diagnostic biomarker for septic AKI (78.8% sensitivity, 87.9% specificity), with plasma levels positively correlating with creatinine (r = 0.725) [166]
Therapeutic	miRNA	Rapid gene network modulation (mimics/antagomirs); clinical trials underway	Off-target effects (single miRNA regulates hundreds of genes); delivery challenges (e.g., poor in vivo stability)	The oligonucleotide therapy RGLS4326 (phase I trial) treats ADPKD by inhibiting MIR17 [167]
	lncRNA	lncRNAs often exhibit cell- or tissue-specific expression (e.g., H19 in placental and tumor tissues) and are closely associated with particular diseases (e.g., cancer), reducing off-target effects	Large molecular size complicates delivery; lncRNAs function via secondary/tertiary structures, yet small-molecule drugs targeting these configurations remain technically immature; low human-mouse lncRNA conservation poses challenges for preclinical studies	Exosome-transmitted lncRNA ARSR confers sunitinib resistance in renal cancer by acting as a ceRNA (sponging MIR34 or MIR449) to activate AXL-STAT3 signaling, representing a therapeutic target for resistance reversal [168]
	circRNA	Acts as miRNA sponges, regulates transcription, or encodes functional peptides, offering diverse therapeutic mechanisms; engineered circRNAs can deliver siRNA, mRNA, or proteins, leveraging their stability for drug delivery	Circularization and large-scale production challenges (low backsplicing efficiency/methods requiring optimization); In vivo delivery hurdles (targeting specificity/immune barriers/cellular uptake limitations)	The circASAP1-HNRNPC-GPX4 axis promotes ccRCC progression by regulating ferroptosis, with high circASAP1 expression indicating poor prognosis and serving as a therapeutic target [169]

Open in a new tab

ncRNAs as autophagy-related diagnostic biomarkers

ncRNAs play a significant role in the pathogenesis of various kidney diseases and demonstrate strong potential as diagnostic and prognostic biomarkers [170–172]. Their stability in biological fluids such as serum and urine makes them attractive candidates for noninvasive diagnostic tools [173,174]. Recent studies have identified specific miRNAs and lncRNAs with altered expression patterns in kidney diseases including AKI and CKD [18,175–177], where their dysregulation shows clear correlation with disease severity and progression, highlighting their potential for early detection and disease monitoring [178–181]. Clinical evidence supports the biomarker potential of ncRNAs. For instance, sepsis patients with AKI exhibit significantly higher serum and urinary MIR452 levels than those without AKI. Although NephroCheck – the only FDA-approved AKI detection test – relies on urinary [TIMP2-IGFBP7], urinary MIR452 shows higher sensitivity (87.23% vs. 61.54%) albeit slightly lower specificity (78.00% vs. 87.18%) [164]. Similarly, LINC00632/ciRS-7 has emerged as a promising multi-functional biomarker in RCC, with its significant overexpression in tumor tissues and biofluids enabling noninvasive detection, while elevated levels correlate with advanced tumor grade, metastatic potential and poorer overall survival [182]. The dysregulation of ncRNAs has been linked to key pathophysiological processes, including inflammatory and fibrotic responses, often involving abnormal regulation of autophagy [9,183–185]. For instance, MIR214 and circ0000953 have been shown to modulate autophagy-related genes and mediate autophagic flux in renal cells, with both being dysregulated in patient renal biopsy samples [133,152].

Therapeutic targeting of autophagy via ncRNAs

Autophagy induction by drugs, such as rapamycin, or inhibition using chloroquine in mice is prevalent in kidney disease-associated research. Translating these findings into clinical trials is challenging due to the common role of autophagy in maintaining the survival and division of various cells. Additionally, autophagy can cause off-target and unintended side effects in other organs [112,114]. Therefore, leveraging the tissue and cell specificities of ncRNAs for precision therapy could reduce these side effects. The clinical application of ncRNAs as therapeutic targets, particularly in regulating autophagy, is a rapidly evolving and promising area of biomedical research.

Several miRNAs regulate autophagy either by directly targeting autophagy-related genes or by modulating signaling pathways that affect autophagic flux. For instance, treatment with curcumin upregulates MIR148 and ADAMTS18 (ADAM metallopeptidase with thrombospondin type 1 motif 18) expression in 786-O cells while decreasing the protein levels of LC3-II:LC3-I. This orchestrated response inhibits autophagy, thereby curbing RCC proliferation [113]. Dihydromyricetin improves autophagy and attenuates renal interstitial fibrosis by modulating the MIR155-5p-PTEN and PI3K-AKT-MTOR signaling pathways [186]. In vitro, pyridoxamine inhibits advanced glycation end products (AGEs) formation, which in turn prevents the expression and activation of TP53-MIR34A induced by AGEs. This consequently restores SIRT1 expression to mitigate podocyte apoptosis [155]. Atrasentan alleviates kidney injury by inhibiting MIR21 expression and fostering cellular autophagy in mice with diabetic kidney disease [154]. In addition, some lncRNAs and circRNAs play similar roles. For example, the total glucosides of paeony can reduce lncRNA HCG18 expression level to facilitate cellular autophagy and suppress apoptosis in IRI-induced AKI [129]. Furthermore, Shensu IV promotes glomerular podocyte autophagy by modulating the expression of lncRNA H19-DIRAS3, thereby exerting protective effects on podocytes [145].

miRNA mimics and inhibitors are primary tools for modulating miRNA expression in therapeutic applications. For instance, MIR365-3p mimics decrease target gene Rheb expression, activate autophagy, and mitigate cell apoptosis induced by CM in NRK-52E cells [124]. Moreover, MIR92A agomir significantly reduces the apoptosis and autophagy in HK2 cells, induced by hypoxia, hypoxia-reoxygenation, and rapamycin, while MIR92A antagomir has opposite effects [121]. Locked Nucleic Acid (LNA)-anti-MIR214 acts as an inhibitor of MIR214, preventing the reduction of ULK1 expression and autophagy damage in diabetic kidneys, thereby reducing kidney hypertrophy and albuminuria [133].

Emerging technologies in ncRNAs-based diagnostics and therapeutics

Emerging technologies, including nanoparticles, clustered regularly interspaced short palindromic repeats (CRISPR), and single-cell sequencing, show promising potential for diagnostics and therapeutics related to ncRNAs.

Nanomedicine-based therapies provide significant advantages in drug delivery by improving drug solubility and reducing off-target effects. An expanding range of engineered nanomaterials shows significant potential for renal disease applications, leveraging their distinctive physicochemical properties to achieve targeted kidney delivery and enhanced therapeutic efficacy [187]. Nanoparticles can either be combined with miRNA inhibitors or drugs to decrease miRNA expression. For example, combining anti-miRNA plasmids with iron oxide/alginate nanoparticles linked to anti-kidney antibodies allows for the targeted delivery to renal tubular cells. The anti-miRNA plasmids released from these nanocomposites effectively inhibited cell proliferation and cyst formation in both cellular and animal models of PKD [188]. Moreover, gold nanoparticles (AuNPs) conjugated with dapagliflozin inhibit apoptosis and fibrosis in DKD through their suppressive effects on MIR192 and MIR21 [189]. Conversely, nanoparticles can also deliver miRNA mimics or drugs to enhance miRNA expression. For example, polyethylenimine nanoparticles (PEI-NPs) carrying MIR146A significantly increases MIR146A expression compared to control groups, while simultaneously reducing renal fibrosis area, decreasing ACTA2 expression, and limiting infiltration of ADGRE1/F4/80⁺ macrophages into the obstructed kidney [190]. Furthermore, dioscin-loaded zein nanoparticles were demonstrated to alleviate LPS-induced acute kidney injury by modulating the MIRLET7I-TLR4 (toll like receptor 4) signaling pathway [191].

CRISPR and its associated Cas enzymes have recently become powerful diagnostic tools [192]. Stevens et al. built on this technology and integrated nanomedicine approaches to develop an innovative nanozyme-based CRISPR diagnostic platform called CrisprZyme. This platform enables quantitative detection of non-coding RNA species with high sensitivity, without the need for preamplification [193]. In parallel developments, Chen and colleagues successfully employed an RNA-targeting CRISPR-Cas13 system (RfxCas13d) to specifically distinguish circular RNAs from their linear mRNA counterparts by designing guide RNAs (gRNAs) that precisely target back-splicing junction (BSJ) sites. The RfxCas13d-BSJ-gRNA system outperforms conventional shRNA-mediated approaches. It achieves more efficient circRNA knockdown and significantly reduces off-target effects on linear mRNAs [194].

Recent breakthroughs in single-cell RNA sequencing (scRNA-seq) have revolutionized the study of ncRNA dynamics in renal pathophysiology, offering single-cell resolution to dissect disease mechanisms [195]. By delineating cell subtype-specific ncRNA expression profiles within the kidney, this approach enables precise identification of disease-specific therapeutic targets and facilitates the rational design of optimized nanomedicine systems. Furthermore, when integrated with CRISPR-based screening or spatial transcriptomics, scRNA-seq can transform our understanding of how ncRNA-autophagy networks are regulated in different renal compartments. This integration will help advance personalized therapeutic strategies. Huang et al. made a significant breakthrough by developing SUPeR-seq (single-cell universal poly(A)-independent RNA sequencing), an innovative method that utilizes random primers containing fixed anchor sequences instead of traditional oligo(dT) primers for cDNA synthesis. This approach demonstrated remarkable sensitivity for circRNA detection at single-cell resolution, identifying 141 circRNA transcripts in individual HEK293 cells and 2,891 in single mouse early embryonic cells [196].

Current challenges

The clinical use of ncRNA-based diagnostic biomarkers and therapeutic targets presents several challenges. Regarding diagnostic biomarkers, ncRNAs are still largely understudied in biological fluids that indicate renal cell-specific autophagic activity. There is a lack of noninvasive tools that reflect autophagic activity in injured kidney cells. Therefore, analyzing the expression profiles of tissue and cell type-specific ncRNAs in biological fluids may provide a promising noninvasive indicator of autophagic activity in kidney cells. Second, there is an urgent need for standardized methods to quantify ncRNA expression in biological fluids. Third, ncRNAs that may act as biomarkers need to be validated in large cohorts to establish their reliability and specificity for various kidney diseases.

From the perspective of diagnostic biomarkers: First, bioinformatic analysis shows that miRNA has multiple potential targets. This hinders the accurate identification of its mechanism of action. Additionally, off-target effects may occur since the target sequences of miRNAs are prevalent across many genes and genomic regions [197]. Moreover, the typically low conservation of lncRNAs across species hinders the identification of their specific functions. This prevents the translation of discoveries made in murine models to human applications, such as lncRNA LFAR1 and lncRNA TSI [18,118]. Second, similar to all RNA treatments, another significant challenge for ncRNA therapy is delivery. Effective delivery vectors require the efficient delivery of ncRNA to target cells and avoidance of triggering immune responses or toxic reactions [198,199]. In contrast, circRNAs such as circBNC2 are highly conserved across species, including in humans and mice [177,200]. Given their stability, tissue specificity, and conservation, circRNAs could be a promising strategy for preventing and precisely treating various diseases when delivered via nanoparticles [201], adeno-associated viruses [202], or exosomes for targeted therapy [203,204]. Third, significant regulatory hurdles must be overcome as ncRNA-based therapies progress toward clinical trials. The long-term safety and efficacy of these therapies must be thoroughly evaluated in clinical settings, which can be complicated by the complexity of ncRNA interactions and their diverse roles in cellular processes [205].

Conclusions and future perspectives

This review provides a comprehensive exploration of how ncRNAs regulate autophagy in the kidney and thus affect disease progression. First, we reviewed the effects of miRNAs, lncRNAs, circRNAs and ceRNA-miRNA axes on the promotion or inhibition of autophagy in RCC, AKI and CKD, which improved or aggravated the progression of the disease. Second, although there are fewer studies, we have also seen similar effects in kidney stone, IgA nephropathy, lupus nephritis and FSGS. Finally, we illustrate the clinical potential of ncRNAs as biomarkers and therapeutic targets for kidney diseases, while also highlighting the development of emerging technologies – such as nanoparticles, CRISPR, and single-cell sequencing – alongside existing challenges.

As a stress-response mechanism, autophagy is activated under various cellular stress conditions – including ROS, ER stress, and drug-induced stress. These stressors can regulate ncRNAs, which in turn may modulate autophagy and contribute to disease pathogenesis, including kidney disease. Key examples include: During ER stress, MIR346 induction stimulates autophagic flux in HeLa cells, providing cytoprotection against stress-induced cell death [206]. lncRNA IGFL2-AS1 is upregulated in sunitinib-resistant RCC cells, where it enhances autophagy by competitively binding HNRNPC to promote TP53INP2 expression, leading to tumor progression [107]. Although systematic classification of stress conditions and related ncRNAs would elucidate molecular pathways in kidney disease, current evidence primarily comes from complex pathological contexts rather than defined stress models. Future research should employ controlled stress paradigms (e.g., tunicamycin for ER stress, H₂O₂ for oxidative stress) to precisely map stress-specific ncRNA signatures and their autophagy-modulating functions in renal pathophysiology.

Additionally, selective autophagy, which includes lipophagy, mitophagy, aggrephagy, and reticulophagy, plays a crucial role in kidney disease, but its effects can vary depending on the context. Lipophagy controls the turnover of lipid droplets in kidney tubular cells. When it is impaired in DKD, it worsens lipotoxicity and fibrosis. Studies have linked a deficiency in autophagy to increased lipid accumulation [207]. Mitophagy maintains mitochondrial quality control, mitigating oxidative stress and inflammation; however, dysregulated mitophagy due to sustained ROS overproduction can paradoxically amplify tubular injury in AKI and CKD [208,209]. HIF1A-BNIP3-mediated reticulophagy helps protect against IRI by degrading stressed ER components. However, if this pathway is overactivated, it may lead to the depletion of essential organelles, indicating the need for careful therapeutic targeting [210]. Recent evidence indicates that ncRNAs can adjust these selective autophagy pathways. They may help restore balance or worsen disease, depending on how they interact with autophagy regulators such as ULK1 and OFD1 [211]. Thus, understanding the spatiotemporal regulation of selective autophagy and its crosstalk with ncRNAs is critical for developing context-specific therapies.

However, while we have noted the protective role of autophagy in kidney disease, it is important to understand that it can also have harmful effects. This balance depends on various factors, including the type of injury and the stage of the disease. For example, in various types of AKI, the pharmacological autophagy inhibitor 3-MA has been shown to worsen cisplatin-induced tubular cell apoptosis while improving LPS-induced renal inflammation [84,87]. Furthermore, during the early phase of AKI, autophagy plays a protective role by clearing damaged organelles and mitigating oxidative stress [212]. However, during the transition from AKI to CKD, or in established CKD, prolonged activation of autophagy may promote renal fibrosis via the FGF2-EGR1 pathway [13,14,213].

Intriguingly, autophagy can also target ncRNAs by participating in ncRNAs clearance, but this area of research has received little attention, and existing evidence is sparse. To date, lncRNA PVT1 is the only lncRNA discovered to be regulated by autophagy. In diabetes, the expression of lncRNA PVT1 is significantly elevated, but the autophagy inhibitor 3-MA markedly reduces lncRNA PVT1 levels [214].

Overall, targeting autophagy-related ncRNAs is a novel and innovative approach that could significantly advance the diagnosis and the treatment of kidney diseases. Through continuous research and innovation, we look forward to developing more effective and safer therapies that will bring new hope to patients.

Funding Statement

This work was supported by grants from the National Natural Science Foundation of China [82170691, 82000651, 82370705 and 82402837], the High Talent Project of Guangdong Province [2023TQ07A687], the Guangdong Basic and Applied Basic Research Foundation [2022A1515012209, 2021A1515010859 and 2024A1515110247], the Research Start-up Funds for High-level Talents in the Affiliated Hospital of Guangdong Medical University [GCC2022044, GCC2024008 and GCC2022046], the Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases [2022B1212030003], and the National Clinical Key Specialty Construction Project (Institute of Nephrology, Affiliated Hospital of Guangdong Medical University), the Science and Technology projects in Guangzhou [202201011108], the Medical Scientific Research Foundation of Guangdong Province of China [A2025041, B2025038, A2024394 and A2023115], the Joint Research Project of Liaoning Provincial Technology Plan [Applied Basic Research Program, 2023-JH2/101700312], the Special Project for Clinical and Basic Sci&Tech Innovation of Guangdong Medical University [GDMULCJC2025233, GDMULCJC2025248].

Disclosure statement

No potential conflict of interest was reported by the author(s).

References

[1].Francis A, Harhay MN, Ong ACM, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. 2024;20(7):473–485. doi: 10.1038/s41581-024-00820-6 [DOI] [PubMed] [Google Scholar]
[2].Taylor SD. Bibliography on nursing research, 1950–1974. Nurs Res. 1975;24(3):207–225. doi: 10.1097/00006199-197505000-00015 [DOI] [PubMed] [Google Scholar]
[3].Leibovich BC, Lohse CM, Crispen PL, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 2010;183(4):1309–1315. doi: 10.1016/j.juro.2009.12.035 [DOI] [PubMed] [Google Scholar]
[4].Lipworth L, Morgans AK, Edwards TL, et al. Renal cell cancer histological subtype distribution differs by race and sex. BJU Int. 2016;117(2):260–265. doi: 10.1111/bju.12950 [DOI] [PubMed] [Google Scholar]
[5].Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet. 2015;385(9981):1975–1982. doi: 10.1016/S0140-6736(14)61601-9 [DOI] [PubMed] [Google Scholar]
[6].Liu WJ, Luo MN, Tan J, et al. Autophagy activation reduces renal tubular injury induced by urinary proteins. Autophagy. 2014;10(2):243–256. doi: 10.4161/auto.27004 [DOI] [PMC free article] [PubMed] [Google Scholar]
[7].Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379(9811):165–180. doi: 10.1016/S0140-6736(11)60178-5 [DOI] [PubMed] [Google Scholar]
[8].Huang XR, Ye L, An N, et al. Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1. Autophagy. 2025;21(1):120–140. doi: 10.1080/15548627.2024.2393926 [DOI] [PMC free article] [PubMed] [Google Scholar]
[9].Kimura T, Isaka Y, Yoshimori T. Autophagy and kidney inflammation. Autophagy. 2017;13(6):997–1003. doi: 10.1080/15548627.2017.1309485 [DOI] [PMC free article] [PubMed] [Google Scholar]
[10].Su L, Zhang J, Gomez H, et al. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2023;19(2):401–414. doi: 10.1080/15548627.2022.2084862 [DOI] [PMC free article] [PubMed] [Google Scholar]
[11].Minami S, Sakai S, Yamamoto T, et al. Fgf21 and autophagy coordinately counteract kidney disease progression during aging and obesity. Autophagy. 2024;20(3):489–504. doi: 10.1080/15548627.2023.2259282 [DOI] [PMC free article] [PubMed] [Google Scholar]
[12].Deng Z, He M, Hu H, et al. Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation. Autophagy. 2024;20(1):151–165. doi: 10.1080/15548627.2023.2252265 [DOI] [PMC free article] [PubMed] [Google Scholar]
[13].Livingston MJ, Shu S, Fan Y, et al. Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis. Autophagy. 2023;19(1):256–277. doi: 10.1080/15548627.2022.2072054 [DOI] [PMC free article] [PubMed] [Google Scholar]
[14].Livingston MJ, Zhang M, Kwon SH, et al. Autophagy activates EGR1 via MAPK/ERK to induce FGF2 in renal tubular cells for fibroblast activation and fibrosis during maladaptive kidney repair. Autophagy. 2024;20(5):1032–1053. doi: 10.1080/15548627.2023.2281156 [DOI] [PMC free article] [PubMed] [Google Scholar]
[15].Huynh C, Ryu J, Lee J, et al. Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases. Nat Rev Nephrol. 2023;19(2):102–122. doi: 10.1038/s41581-022-00648-y [DOI] [PubMed] [Google Scholar]
[16].Shi Y, Tao M, Ma X, et al. Delayed treatment with an autophagy inhibitor 3-MA alleviates the progression of hyperuricemic nephropathy. Cell Death Dis. 2020;11(6):467. doi: 10.1038/s41419-020-2673-z [DOI] [PMC free article] [PubMed] [Google Scholar]
[17].Zhu H, Wu H, Liu X, et al. Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy. 2009;5(6):816–823. doi: 10.4161/auto.9064 [DOI] [PMC free article] [PubMed] [Google Scholar]
[18].Wang P, Luo ML, Song E, et al. Long noncoding RNA lnc-TSI inhibits renal fibrogenesis by negatively regulating the TGF-beta/Smad3 pathway. Sci Transl Med. 2018;10(462). doi: 10.1126/scitranslmed.aat2039 [DOI] [PubMed] [Google Scholar]
[19].Ward M, McEwan C, Mills JD, et al. Conservation and tissue-specific transcription patterns of long noncoding RNAs. J Hum Transcriptome. 2015;1(1):2–9. doi: 10.3109/23324015.2015.1077591 [DOI] [PMC free article] [PubMed] [Google Scholar]
[20].Ying L, Huang Y, Chen H, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–411. doi: 10.1039/c2mb25386k [DOI] [PubMed] [Google Scholar]
[21].Huang R, Zhang Y, Han B, et al. Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG. Autophagy. 2017;13(10):1722–1741. doi: 10.1080/15548627.2017.1356975 [DOI] [PMC free article] [PubMed] [Google Scholar]
[22].Zhang P, Wu W, Chen Q, et al. Non-coding RNAs and their integrated networks. J Integr Bioinform. 2019;16(3). doi: 10.1515/jib-2019-0027 [DOI] [PMC free article] [PubMed] [Google Scholar]
[23].Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–227. doi: 10.1038/nature07672 [DOI] [PMC free article] [PubMed] [Google Scholar]
[24].Cabili MN, Trapnell C, Goff L, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915–1927. doi: 10.1101/gad.17446611 [DOI] [PMC free article] [PubMed] [Google Scholar]
[25].Cerutti P, Holt JW, Miller N. Detection and determination of 5,6-dihydrouridine and 4-thiouridine in transfer ribonucleic acid from different sources. J Mol Biol. 1968;34(3):505–518. doi: 10.1016/0022-2836(68)90176-9 [DOI] [PubMed] [Google Scholar]
[26].Chen Q, Meng X, Liao Q, et al. Versatile interactions and bioinformatics analysis of noncoding RNAs. Brief Bioinform. 2019;20(5):1781–1794. doi: 10.1093/bib/bby050 [DOI] [PubMed] [Google Scholar]
[27].Hombach S, Kretz M. Non-coding RNAs: classification, biology and functioning. Adv Exp Med Biol. 2016;937(3–17). doi: 10.1007/978-3-319-42059-2_1 [DOI] [PubMed] [Google Scholar]
[28].Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–157. doi: 10.1261/rna.035667.112 [DOI] [PMC free article] [PubMed] [Google Scholar]
[29].Farazi TA, Hoell JI, Morozov P, et al. MicroRNAs in human cancer. Adv Exp Med Biol. 2013;774(1–20). doi: 10.1007/978-94-007-5590-1_1 [DOI] [PMC free article] [PubMed] [Google Scholar]
[30].Bartel DP. Metazoan microRNAs. Cell. 2018;173(1):20–51. doi: 10.1016/j.cell.2018.03.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
[31].Wang P, Chen W, Zhao S, et al. The role of lncRNA-regulated autophagy in AKI. Biofactors. 2023;49(5):1010–1021. doi: 10.1002/biof.1980 [DOI] [PubMed] [Google Scholar]
[32].Sauvageau M. Diverging RNPs: toward understanding lncRNA-protein interactions and functions. Adv Exp Med Biol. 2019;1203(285–312). doi: 10.1007/978-3-030-31434-7_10 [DOI] [PubMed] [Google Scholar]
[33].Elguindy MM, Kopp F, Goodarzi M, et al. PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD. Elife. 2019;8. doi: 10.7554/eLife.48625 [DOI] [PMC free article] [PubMed] [Google Scholar]
[34].Pandey PR, Rout PK, Das A, et al. Rpad (RNase R treatment, polyadenylation, and poly(A)+ RNA depletion) method to isolate highly pure circular RNA. Methods. 2019;155(41):41–48. doi: 10.1016/j.ymeth.2018.10.022 [DOI] [PMC free article] [PubMed] [Google Scholar]
[35].Zhong Y, Du Y, Yang X, et al. Circular RNAs function as ceRnas to regulate and control human cancer progression. Mol Cancer. 2018;17(1):79. doi: 10.1186/s12943-018-0827-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
[36].Zhu P, Zhu X, Wu J, et al. Il-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat Immunol. 2019;20(2):183–194. doi: 10.1038/s41590-018-0297-6 [DOI] [PubMed] [Google Scholar]
[37].Chen Y, Yang F, Fang E, et al. Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes. Cell Death Differ. 2019;26(7):1346–1364. doi: 10.1038/s41418-018-0220-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
[38].Yang ZG, Awan FM, Du WW, et al. The circular RNA interacts with STAT3, increasing its nuclear translocation and wound repair by modulating Dnmt3a and miR-17 function. Mol Ther. 2017;25(9):2062–2074. doi: 10.1016/j.ymthe.2017.05.022 [DOI] [PMC free article] [PubMed] [Google Scholar]
[39].Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66(1):22–37 e9. doi: 10.1016/j.molcel.2017.02.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
[40].Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–131. doi: 10.1016/j.ceb.2009.11.014 [DOI] [PMC free article] [PubMed] [Google Scholar]
[41].Mijaljica D, Prescott M, Devenish RJ. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy. 2011;7(7):673–682. doi: 10.4161/auto.7.7.14733 [DOI] [PubMed] [Google Scholar]
[42].Massey A, Kiffin R, Cuervo AM. Pathophysiology of chaperone-mediated autophagy. Int J Biochem Cell Biol. 2004;36(12):2420–2434. doi: 10.1016/j.biocel.2004.04.010 [DOI] [PubMed] [Google Scholar]
[43].Tekirdag K, Cuervo AM. Chaperone-mediated autophagy and endosomal microautophagy: joint by a chaperone. J Biol Chem. 2018;293(15):5414–5424. doi: 10.1074/jbc.R117.818237 [DOI] [PMC free article] [PubMed] [Google Scholar]
[44].Vargas JNS, Hamasaki M, Kawabata T, et al. The mechanisms and roles of selective autophagy in mammals. Nat Rev Mol Cell Biol. 2023;24(3):167–185. doi: 10.1038/s41580-022-00542-2 [DOI] [PubMed] [Google Scholar]
[45].Lamark T, Johansen T. Mechanisms of selective autophagy. Annu Rev Cell Dev Biol. 2021;37(143–69):143–169. doi: 10.1146/annurev-cellbio-120219-035530 [DOI] [PubMed] [Google Scholar]
[46].Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol. 2009;335(1–32). doi: 10.1007/978-3-642-00302-8_1 [DOI] [PMC free article] [PubMed] [Google Scholar]
[47].Chiu HC, Richart S, Lin FY, et al. The interplay of reovirus with autophagy. Biomed Res Int. 2014;2014(483657):1–8. doi: 10.1155/2014/483657 [DOI] [PMC free article] [PubMed] [Google Scholar]
[48].Sergin I, Razani B. Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis. Trends Endocrinol Metab. 2014;25(5):225–234. doi: 10.1016/j.tem.2014.03.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
[49].Stead ER, Castillo-Quan JI, Miguel VEM, et al. Agephagy - adapting autophagy for health during aging. Front Cell Dev Biol. 2019;7(308). doi: 10.3389/fcell.2019.00308 [DOI] [PMC free article] [PubMed] [Google Scholar]
[50].Jung CH, Ro SH, Cao J, et al. mTOR regulation of autophagy. FEBS Lett. 2010;584(7):1287–1295. doi: 10.1016/j.febslet.2010.01.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
[51].Alers S, Loffler AS, Wesselborg S, et al. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol. 2012;32(1):2–11. doi: 10.1128/MCB.06159-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
[52].Tanida I, Ueno T, Kominami E. Lc3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503–2518. doi: 10.1016/j.biocel.2004.05.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
[53].Kim J, Kundu M, Viollet B, et al. Ampk and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132–141. doi: 10.1038/ncb2152 [DOI] [PMC free article] [PubMed] [Google Scholar]
[54].Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280–293. doi: 10.1016/j.molcel.2010.09.023 [DOI] [PMC free article] [PubMed] [Google Scholar]
[55].Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728–741. doi: 10.1016/j.cell.2011.10.026 [DOI] [PubMed] [Google Scholar]
[56].Maiuri MC, Le Toumelin G, Criollo A, et al. Functional and physical interaction between Bcl-x(L) and a BH3-like domain in Beclin-1. Embo J. 2007;26(10):2527–2539. doi: 10.1038/sj.emboj.7601689 [DOI] [PMC free article] [PubMed] [Google Scholar]
[57].Carriere A, Romeo Y, Acosta-Jaquez HA, et al. Erk1/2 phosphorylate raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem. 2011;286(1):567–577. doi: 10.1074/jbc.M110.159046 [DOI] [PMC free article] [PubMed] [Google Scholar]
[58].Kim JH, Hong SK, Wu PK, et al. Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels. Exp Cell Res. 2014;327(2):340–352. doi: 10.1016/j.yexcr.2014.08.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
[59].He Y, She H, Zhang T, et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol. 2018;217(1):315–328. doi: 10.1083/jcb.201701049 [DOI] [PMC free article] [PubMed] [Google Scholar]
[60].McClung JM, Judge AR, Powers SK, et al. p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol. 2010;298(3):C542–9. doi: 10.1152/ajpcell.00192.2009 [DOI] [PMC free article] [PubMed] [Google Scholar]
[61].Lin R, Feng J, Dong S, et al. Regulation of autophagy of prostate cancer cells by beta-catenin signaling. Cell Physiol Biochem. 2015;35(3):926–932. doi: 10.1159/000369749 [DOI] [PubMed] [Google Scholar]
[62].Crighton D, Wilkinson S, O’Prey J, et al. Dram, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126(1):121–134. doi: 10.1016/j.cell.2006.05.034 [DOI] [PubMed] [Google Scholar]
[63].Jia J, Abudu YP, Claude-Taupin A, et al. Galectins control mTOR in response to endomembrane damage. Mol Cell. 2018;70(1):120–35 e8. doi: 10.1016/j.molcel.2018.03.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
[64].Lee IH, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105(9):3374–3379. doi: 10.1073/pnas.0712145105 [DOI] [PMC free article] [PubMed] [Google Scholar]
[65].Keith B, Johnson RS, Simon MC. HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2011;12(1):9–22. doi: 10.1038/nrc3183 [DOI] [PMC free article] [PubMed] [Google Scholar]
[66].White E, Mehnert JM, Autophagy CC. Metabolism, and cancer. Clin Cancer Res. 2015;21(22):5037–5046. doi: 10.1158/1078-0432.CCR-15-0490 [DOI] [PMC free article] [PubMed] [Google Scholar]
[67].White E. The role for autophagy in cancer. J Clin Invest. 2015;125(1):42–46. doi: 10.1172/JCI73941 [DOI] [PMC free article] [PubMed] [Google Scholar]
[68].Janku F, McConkey DJ, Hong DS, et al. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011;8(9):528–539. doi: 10.1038/nrclinonc.2011.71 [DOI] [PubMed] [Google Scholar]
[69].Cao Q, Bai P. Role of autophagy in renal cancer. J Cancer. 2019;10(11):2501–2509. doi: 10.7150/jca.29285 [DOI] [PMC free article] [PubMed] [Google Scholar]
[70].Sun J, Ding J, Yue H, et al. Hypoxia-induced BNIP3 facilitates the progression and metastasis of uveal melanoma by driving metabolic reprogramming. Autophagy. 2025;21(1):191–209. doi: 10.1080/15548627.2024.2395142 [DOI] [PMC free article] [PubMed] [Google Scholar]
[71].Murugesan T, Rajajeyabalachandran G, Kumar S, et al. Targeting HIF-2alpha as therapy for advanced cancers. Drug Discov Today. 2018;23(7):1444–1451. doi: 10.1016/j.drudis.2018.05.003 [DOI] [PubMed] [Google Scholar]
[72].Ferro F, Servais S, Besson P, et al. Autophagy and mitophagy in cancer metabolic remodelling. Semin Cell Dev Biol. 2020;98(129):129–138. doi: 10.1016/j.semcdb.2019.05.029 [DOI] [PubMed] [Google Scholar]
[73].Gao L, Chen Y. Autophagy controls programmed death-ligand 1 expression on cancer cells (review). Biomed Rep. 2021;15(4):84. doi: 10.3892/br.2021.1460 [DOI] [PMC free article] [PubMed] [Google Scholar]
[74].Messai Y, Noman MZ, Hasmim M, et al. Itpr1 protects renal cancer cells against natural killer cells by inducing autophagy. Cancer Res. 2014;74(23):6820–6832. doi: 10.1158/0008-5472.CAN-14-0303 [DOI] [PubMed] [Google Scholar]
[75].Messai Y, Noman MZ, Janji B, et al. The autophagy sensor ITPR1 protects renal carcinoma cells from NK-mediated killing. Autophagy. 2015:0. doi: 10.1080/15548627.2015.1017194 [DOI] [PubMed] [Google Scholar]
[76].White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 2012;12(6):401–410. doi: 10.1038/nrc3262 [DOI] [PMC free article] [PubMed] [Google Scholar]
[77].Chien CT, Shyue SK, Lai MK. Bcl-xL augmentation potentially reduces ischemia/reperfusion induced proximal and distal tubular apoptosis and autophagy. Transplantation. 2007;84(9):1183–1190. doi: 10.1097/01.tp.0000287334.38933.e3 [DOI] [PubMed] [Google Scholar]
[78].Suzuki C, Isaka Y, Takabatake Y, et al. Participation of autophagy in renal ischemia/reperfusion injury. Biochem Biophys Res Commun. 2008;368(1):100–106. doi: 10.1016/j.bbrc.2008.01.059 [DOI] [PubMed] [Google Scholar]
[79].Tang C, Han H, Yan M, et al. Pink1-Prkn/Park2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury. Autophagy. 2018;14(5):880–897. doi: 10.1080/15548627.2017.1405880 [DOI] [PMC free article] [PubMed] [Google Scholar]
[80].He L, Livingston MJ, Dong Z. Autophagy in acute kidney injury and repair. Nephron Clin Pract. 2014;127(1–4):56–60. doi: 10.1159/000363677 [DOI] [PMC free article] [PubMed] [Google Scholar]
[81].Jiang M, Liu K, Luo J, et al. Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. Am J Pathol. 2010;176(3):1181–1192. doi: 10.2353/ajpath.2010.090594 [DOI] [PMC free article] [PubMed] [Google Scholar]
[82].Leventhal JS, Ni J, Osmond M, et al. Autophagy limits endotoxemic acute kidney injury and alters renal tubular epithelial cell cytokine expression. PLOS ONE. 2016;11(3):e0150001. doi: 10.1371/journal.pone.0150001 [DOI] [PMC free article] [PubMed] [Google Scholar]
[83].Mei S, Livingston M, Hao J, et al. Autophagy is activated to protect against endotoxic acute kidney injury. Sci Rep. 2016;6(22171). doi: 10.1038/srep22171 [DOI] [PMC free article] [PubMed] [Google Scholar]
[84].Wu Y, Zhang Y, Wang L, et al. The role of autophagy in kidney inflammatory injury via the NF-kappaB route induced by LPS. Int J Med Sci. 2015;12(8):655–667. doi: 10.7150/ijms.12460 [DOI] [PMC free article] [PubMed] [Google Scholar]
[85].Takahashi W, Watanabe E, Fujimura L, et al. Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. Crit Care. 2013;17(4):R160. doi: 10.1186/cc12839 [DOI] [PMC free article] [PubMed] [Google Scholar]
[86].Sunahara S, Watanabe E, Hatano M, et al. Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model. Sci Rep. 2018;8(1):1050. doi: 10.1038/s41598-018-19350-w [DOI] [PMC free article] [PubMed] [Google Scholar]
[87].Periyasamy-Thandavan S, Jiang M, Wei Q, et al. Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. Kidney Int. 2008;74(5):631–640. doi: 10.1038/ki.2008.214 [DOI] [PubMed] [Google Scholar]
[88].Lee SY, Kim SI, Choi ME. Therapeutic targets for treating fibrotic kidney diseases. Transl Res. 2015;165(4):512–530. doi: 10.1016/j.trsl.2014.07.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
[89].Ammirati AL. Chronic kidney disease. Rev Assoc Med Bras. 2020;66(Suppl 1):s03–s9. doi: 10.1590/1806-9282.66.S1.3 [DOI] [PubMed] [Google Scholar]
[90].Liu N, Shi Y, Zhuang S. Autophagy in chronic kidney diseases. Kidney Dis (Basel). 2016;2(1):37–45. doi: 10.1159/000444841 [DOI] [PMC free article] [PubMed] [Google Scholar]
[91].Lin TA, Wu VC, Wang CY. Autophagy in chronic kidney diseases. Cells. 2019;8(1):61. doi: 10.3390/cells8010061 [DOI] [PMC free article] [PubMed] [Google Scholar]
[92].De Rechter S, Decuypere JP, Ivanova E, et al. Autophagy in renal diseases. Pediatr Nephrol. 2016;31(5):737–752. doi: 10.1007/s00467-015-3134-2 [DOI] [PubMed] [Google Scholar]
[93].Koch EAT, Nakhoul R, Nakhoul F, et al. Autophagy in diabetic nephropathy: a review. Int Urol Nephrol. 2020;52(9):1705–1712. doi: 10.1007/s11255-020-02545-4 [DOI] [PubMed] [Google Scholar]
[94].Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2016;12(2):73–81. doi: 10.1038/nrneph.2015.173 [DOI] [PubMed] [Google Scholar]
[95].Nam SA, Kim WY, Kim JW, et al. Autophagy attenuates tubulointerstitial fibrosis through regulating transforming growth factor-beta and NLRP3 inflammasome signaling pathway. Cell Death Dis. 2019;10(2):78. doi: 10.1038/s41419-019-1356-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
[96].Belibi F, Zafar I, Ravichandran K, et al. Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD). Am J Physiol Renal Physiol. 2011;300(5):F1235–43. doi: 10.1152/ajprenal.00348.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
[97].Zafar I, Ravichandran K, Belibi FA, et al. Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease. Kidney Int. 2010;78(8):754–761. doi: 10.1038/ki.2010.250 [DOI] [PubMed] [Google Scholar]
[98].Zhu P, Sieben CJ, Xu X, et al. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Hum Mol Genet. 2017;26(1):158–172. doi: 10.1093/hmg/ddw376 [DOI] [PMC free article] [PubMed] [Google Scholar]
[99].Mikhaylova O, Stratton Y, Hall D, et al. VHL-regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 2012;21(4):532–546. doi: 10.1016/j.ccr.2012.02.019 [DOI] [PMC free article] [PubMed] [Google Scholar]
[100].Hall DP, Cost NG, Hegde S, et al. Trpm3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma. Cancer Cell. 2014;26(5):738–753. doi: 10.1016/j.ccell.2014.09.015 [DOI] [PMC free article] [PubMed] [Google Scholar]
[101].Zheng B, Zhu H, Gu D, et al. miRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib. Biochem Biophys Res Commun. 2015;459(2):234–239. doi: 10.1016/j.bbrc.2015.02.084 [DOI] [PubMed] [Google Scholar]
[102].Long JS, Ryan KM. New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy. Oncogene. 2012;31(49):5045–5060. doi: 10.1038/onc.2012.7 [DOI] [PubMed] [Google Scholar]
[103].Gao C, Peng FH, Peng LK. MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1. Neoplasma. 2014;61(6):680–689. doi: 10.4149/neo_2014_083 [DOI] [PubMed] [Google Scholar]
[104].Patergnani S, Guzzo S, Mangolini A, et al. The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells. Exp Cell Res. 2020;395(1):112190. doi: 10.1016/j.yexcr.2020.112190 [DOI] [PubMed] [Google Scholar]
[105].Su Y, Lu J, Chen X, et al. Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway. J Cancer Res Clin Oncol. 2019;145(3):573–588. doi: 10.1007/s00432-018-2808-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
[106].Wang B, Wei Y, Han T, et al. LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy. Eur J Med Res. 2024;29(1):103. doi: 10.1186/s40001-024-01690-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
[107].Pan Y, Lu X, Shu G, et al. Extracellular vesicle-mediated transfer of lncRNA IGFL2-AS1 confers sunitinib resistance in renal cell carcinoma. Cancer Res. 2023;83(1):103–116. doi: 10.1158/0008-5472.CAN-21-3432 [DOI] [PMC free article] [PubMed] [Google Scholar]
[108].Yang X, Zhang Y, Fan H. Downregulation of SBF2-AS1 functions as a tumor suppressor in clear cell renal cell carcinoma by inhibiting miR-338-3p-targeted ETS1. Cancer Gene Ther. 2021;28(7–8):813–827. doi: 10.1038/s41417-020-0197-4 [DOI] [PubMed] [Google Scholar]
[109].Jin Y, Huang R, Xia Y, et al. Long noncoding RNA KIF9-AS1 regulates transforming growth factor-beta and autophagy signaling to enhance renal cell carcinoma chemoresistance via microRNA-497-5p. DNA Cell Biol. 2020;39(7):1096–1103. doi: 10.1089/dna.2020.5453 [DOI] [PubMed] [Google Scholar]
[110].Li R, Luo S, Zhang D. Circular RNA hsa_circ_0054537 sponges miR-130a-3p to promote the progression of renal cell carcinoma through regulating cMet pathway. Gene. 2020;754(144811):144811. doi: 10.1016/j.gene.2020.144811 [DOI] [PubMed] [Google Scholar]
[111].Pei L, Lv X, Jia G, et al. Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2). Bioengineered. 2021;12(1):8279–8295. doi: 10.1080/21655979.2021.1984002 [DOI] [PMC free article] [PubMed] [Google Scholar]
[112].Yan L, Liu G, Cao H, et al. Hsa_circ_0035483 sponges hsa-miR-335 to promote the gemcitabine-resistance of human renal cancer cells by autophagy regulation. Biochem Biophys Res Commun. 2019;519(1):172–178. doi: 10.1016/j.bbrc.2019.08.093 [DOI] [PubMed] [Google Scholar]
[113].Xu B, Yuan CW, Zhang JE. Curcumin inhibits proliferation of renal cell carcinoma in vitro and in vivo by regulating miR-148/ADAMTS18 through suppressing autophagy. Chin J Integr Med. 2023;29(8):699–706. doi: 10.1007/s11655-022-3690-9 [DOI] [PubMed] [Google Scholar]
[114].Liu X, Hong Q, Wang Z, et al. MiR-21 inhibits autophagy by targeting Rab11a in renal ischemia/reperfusion. Exp Cell Res. 2015;338(1):64–69. doi: 10.1016/j.yexcr.2015.08.010 [DOI] [PubMed] [Google Scholar]
[115].Wang IK, Sun KT, Tsai TH, et al. MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury. Life Sci. 2015;136(133):133–141. doi: 10.1016/j.lfs.2015.07.002 [DOI] [PubMed] [Google Scholar]
[116].Shao X, Zhang S, Tang Y, et al. Micro RNA-30b (inhibitor) nanoparticles suppressed the lipopolysaccharide (LPS)-induced acute kidney injury. IET Nanobiotechnol. 2019;13(9):923–927. doi: 10.1049/iet-nbt.2019.0110 [DOI] [PMC free article] [PubMed] [Google Scholar]
[117].Liu XJ, Hong Q, Wang Z, et al. MicroRNA-34a suppresses autophagy in tubular epithelial cells in acute kidney injury. Am J Nephrol. 2015;42(2):168–175. doi: 10.1159/000439185 [DOI] [PubMed] [Google Scholar]
[118].Liu X, Li Q, Sun L, et al. miR-30e-5p regulates autophagy and apoptosis by targeting Beclin1 involved in contrast-induced acute kidney injury. Curr Med Chem. 2021;28(38):7974–7984. doi: 10.2174/0929867328666210526125023 [DOI] [PubMed] [Google Scholar]
[119].Zhao P, Zhu Y, Sun L, et al. Circulating exosomal miR-1-3p from rats with myocardial infarction plays a protective effect on contrast-induced nephropathy via targeting ATG13 and activating the AKT signaling pathway. Int J Biol Sci. 2021;17(4):972–985. doi: 10.7150/ijbs.55887 [DOI] [PMC free article] [PubMed] [Google Scholar]
[120].Liu Y, Xiao J, Sun J, et al. Atg7 promotes autophagy in sepsis‑induced acute kidney injury and is inhibited by miR‑526b. Mol Med Rep. 2020;21(5):2193–2201. doi: 10.3892/mmr.2020.11001 [DOI] [PMC free article] [PubMed] [Google Scholar]
[121].Ma M, Li H, Yin S, et al. Overexpression of miR-92a attenuates kidney ischemia-reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy. Cell Mol Biol Lett. 2023;28(1):20. doi: 10.1186/s11658-023-00430-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
[122].Chen Y, Zhang C, Du Y, et al. Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6. Chin Med J (Engl). 2022;135(20):2467–2477. doi: 10.1097/CM9.0000000000002377 [DOI] [PMC free article] [PubMed] [Google Scholar]
[123].Dong Y, Han X, Yang Y, et al. miR-506-3p induces autophagy of renal tubular epithelial cells in sepsis through targeting PI3K pathway. Aging (Albany NY). 2023;15(11):4734–4745. doi: 10.18632/aging.204759 [DOI] [PMC free article] [PubMed] [Google Scholar]
[124].Wu T, Zhu W, Duan R, et al. Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p. J Nanobiotechnology. 2024;22(1):666. doi: 10.1186/s12951-024-02928-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
[125].Xiang J, Jiang T, Zhang W, et al. Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy through microRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Cell Res. 2019;378(2):198–205. doi: 10.1016/j.yexcr.2019.03.019 [DOI] [PubMed] [Google Scholar]
[126].Wang IK, Palanisamy K, Sun KT, et al. The functional interplay of lncRNA EGOT and HuR regulates hypoxia-induced autophagy in renal tubular cells. J Cell Biochem. 2020;121(11):4522–4534. doi: 10.1002/jcb.29669 [DOI] [PubMed] [Google Scholar]
[127].Ouyang X, He Z, Fang H, et al. A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway. Mol Ther. 2023;31(6):1722–1738. doi: 10.1016/j.ymthe.2022.09.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
[128].Yang N, Wang H, Zhang L, et al. Long non-coding RNA SNHG14 aggravates LPS-induced acute kidney injury through regulating miR-495-3p/HIPK1. Acta Biochim Biophys Sin (Shanghai). 2021;53(6):719–728. doi: 10.1093/abbs/gmab034 [DOI] [PubMed] [Google Scholar]
[129].Zhao W, Zhang Y, Zhang M, et al. Effects of total glucosides of paeony on acute renal injury following ischemia-reperfusion via the lncRNA HCG18/miR-16-5p/Bcl-2 axis. Immunobiology. 2022;227(2):152179. doi: 10.1016/j.imbio.2022.152179 [DOI] [PubMed] [Google Scholar]
[130].Chang X, Zhang P, Xu XX, et al. Total glucosides of paeony inhibited autophagy and improved acute kidney injury induced by ischemia-reperfusion via the lncRNA TUG1/miR-29a/PTEN axis. Drug Des Devel Ther. 2021;15(2229):2229–2242. doi: 10.2147/DDDT.S286606 [DOI] [PMC free article] [PubMed] [Google Scholar]
[131].Han D, Fang R, Shi R, et al. LncRNA NKILA knockdown promotes cell viability and represses cell apoptosis, autophagy and inflammation in lipopolysaccharide-induced sepsis model by regulating miR-140-5p/CLDN2 axis. Biochem Biophys Res Commun. 2021;559(8):8–14. doi: 10.1016/j.bbrc.2021.04.074 [DOI] [PubMed] [Google Scholar]
[132].Liu D, Liu Y, Zheng X, et al. c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia-reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/beta-catenin pathway. Cell Death Dis. 2021;12(2):191. doi: 10.1038/s41419-021-03466-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
[133].Ma Z, Li L, Livingston MJ, et al. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. J Clin Invest. 2020;130(9):5011–5026. doi: 10.1172/JCI135536 [DOI] [PMC free article] [PubMed] [Google Scholar]
[134].Zhang Y, Zhao S, Wu D, et al. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy. J Diabetes Res. 2018;2018(4728645):1–11. doi: 10.1155/2018/4728645 [DOI] [PMC free article] [PubMed] [Google Scholar]
[135].Zhuang L, Ge X, Hu X, et al. MiR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8. BMC Nephrol. 2022;23(1):89. doi: 10.1186/s12882-022-02716-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
[136].Kato M, Abdollahi M, Tunduguru R, et al. MiR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1. Commun Biol. 2021;4(1):30. doi: 10.1038/s42003-020-01516-w [DOI] [PMC free article] [PubMed] [Google Scholar]
[137].Liu Y, Dong ZJ, Song JW, et al. MicroRNA-122-5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3. Exp Cell Res. 2022;411(2):113017. doi: 10.1016/j.yexcr.2022.113017 [DOI] [PubMed] [Google Scholar]
[138].Yang S, Abdulla R, Lu C, et al. Inhibition of microRNA-376b protects against renal interstitial fibrosis via inducing macrophage autophagy by upregulating Atg5 in mice with chronic kidney disease. Kidney Blood Press Res. 2018;43(6):1749–1764. doi: 10.1159/000495394 [DOI] [PubMed] [Google Scholar]
[139].Jianbing H, Xiaotian L, Jie T, et al. The effect of allograft inflammatory factor-1 on inflammation, oxidative stress, and autophagy via miR-34a/ATG4B pathway in diabetic kidney disease. Oxid Med Cell Longev. 2022;2022(1668000). doi: 10.1155/2022/1668000 [DOI] [PMC free article] [PubMed] [Google Scholar]
[140].Cai X, Zou F, Xuan R, et al. Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy via the tumour necrosis factor receptor-associated factor 6/Akt axis. Endocr J. 2021;68(7):817–828. doi: 10.1507/endocrj.EJ20-0619 [DOI] [PubMed] [Google Scholar]
[141].Huang H, Liu H, Tang J, et al. M2 macrophage-derived exosomal miR-25-3p improves high glucose-induced podocytes injury through activation autophagy via inhibiting DUSP1 expression. IUBMB Life. 2020;72(12):2651–2662. doi: 10.1002/iub.2393 [DOI] [PubMed] [Google Scholar]
[142].Fan WX, Wen XL, Xiao H, et al. MicroRNA-29a enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis by targeting heme oxygenase-1. Eur Rev Med Pharmacol Sci. 2018;22(24):8909–8917. doi: 10.26355/eurrev_201812_16660 [DOI] [PubMed] [Google Scholar]
[143].Yoon YM, Go G, Yoon S, et al. Melatonin treatment improves renal fibrosis via miR-4516/SIAH3/PINK1 axis. Cells. 2021;10(7):1682. doi: 10.3390/cells10071682 [DOI] [PMC free article] [PubMed] [Google Scholar]
[144].Su PP, Liu DW, Zhou SJ, et al. Down-regulation of RISA improves podocyte injury by enhancing autophagy in diabetic nephropathy. Mil Med Res. 2022;9(1):23. doi: 10.1186/s40779-022-00385-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
[145].Huang Y, Huang Y, Zhou Y, et al. Shensu IV prevents glomerular podocyte injury in nephrotic rats via promoting lncRNA H19/DIRAS3-mediated autophagy. Biosci Rep. 2021;41(5). doi: 10.1042/BSR20203362 [DOI] [PMC free article] [PubMed] [Google Scholar]
[146].Guo F, Wang W, Song Y, et al. LncRNA SNHG17 knockdown promotes parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1. Cell Cycle. 2020;19(16):1997–2006. doi: 10.1080/15384101.2020.1783481 [DOI] [PMC free article] [PubMed] [Google Scholar]
[147].Qi C, Liang T, Lin J, et al. Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells. Biochem Biophys Res Commun. 2023;644(95):95–104. doi: 10.1016/j.bbrc.2023.01.013 [DOI] [PubMed] [Google Scholar]
[148].Jin J, Gong J, Zhao L, et al. LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway. Acta Biochim Pol. 2021;68(4):619–625. doi: 10.18388/abp.2020_5483 [DOI] [PubMed] [Google Scholar]
[149].Yang N, Zhang Y, Ren P, et al. LncRNA AA465934 improves podocyte injury by promoting tristetraprolin-mediated HMGB1 downregulation in diabetic nephropathy. Mol Cell Biol. 2024;44(3):87–102. doi: 10.1080/10985549.2024.2325527 [DOI] [PMC free article] [PubMed] [Google Scholar]
[150].Cai Y, Chen S, Jiang X, et al. LncRNA X inactive specific transcript exerts a protective effect on high glucose-induced podocytes by promoting the podocyte autophagy via miR-30d-5p/BECN-1 axis. Int J Endocrinol. 2023;2023(3187846):1–12. doi: 10.1155/2023/3187846 [DOI] [PMC free article] [PubMed] [Google Scholar]
[151].Zhang Y, Chang B, Zhang J, et al. LncRNA SOX2OT alleviates the high glucose-induced podocytes injury through autophagy induction by the miR-9/SIRT1 axis. Exp Mol Pathol. 2019;110(104283):104283. doi: 10.1016/j.yexmp.2019.104283 [DOI] [PubMed] [Google Scholar]
[152].Liu X, Jiang L, Zeng H, et al. Circ-0000953 deficiency exacerbates podocyte injury and autophagy disorder by targeting Mir665-3p-Atg4b in diabetic nephropathy. Autophagy. 2024;20(5):1072–1097. doi: 10.1080/15548627.2023.2286128 [DOI] [PMC free article] [PubMed] [Google Scholar]
[153].Wang Y, Zheng ZJ, Jia YJ, et al. Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease. J Transl Med. 2018;16(1):146. doi: 10.1186/s12967-018-1486-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
[154].Wang J, Shen L, Hong H, et al. Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis. Eur J Pharmacol. 2019;852(142):142–150. doi: 10.1016/j.ejphar.2019.03.013 [DOI] [PubMed] [Google Scholar]
[155].Liang Y, Liu H, Zhu J, et al. Inhibition of p53/miR-34a/SIRT1 axis ameliorates podocyte injury in diabetic nephropathy. Biochem Biophys Res Commun. 2021;559(48):48–55. doi: 10.1016/j.bbrc.2021.04.025 [DOI] [PubMed] [Google Scholar]
[156].Feng Y, Chen S, Xu J, et al. Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy. Mol Med Rep. 2018;18(4):3657–3664. doi: 10.3892/mmr.2018.9412 [DOI] [PMC free article] [PubMed] [Google Scholar]
[157].Chen K, Yu B, Liao J. Lncrna sox2ot alleviates mesangial cell proliferation and fibrosis in diabetic nephropathy via akt/mTOR-mediated autophagy. Mol Med. 2021;27(1):71. doi: 10.1186/s10020-021-00310-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
[158].Xu J, Deng Y, Wang Y, et al. Spag5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell Prolif. 2020;53(2):e12738. doi: 10.1111/cpr.12738 [DOI] [PMC free article] [PubMed] [Google Scholar]
[159].Chen X, Zhang XB, Li DJ, et al. MiR-155 facilitates calcium oxalate crystal-induced HK-2 cell injury via targeting PI3K associated autophagy. Exp Mol Pathol. 2020;115(104450):104450. doi: 10.1016/j.yexmp.2020.104450 [DOI] [PubMed] [Google Scholar]
[160].Shi J, Duan J, Gong H, et al. Exosomes from miR-20b-3p-overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney. J Cell Mol Med. 2019;23(11):7268–7278. doi: 10.1111/jcmm.14555 [DOI] [PMC free article] [PubMed] [Google Scholar]
[161].Yu M, Shen X, He W, et al. Mesangial cell-derived exosomal miR-4455 induces podocyte injury in IgA nephropathy by targeting ULK2. Oxid Med Cell Longev. 2022;2022(1740770). doi: 10.1155/2022/1740770 [DOI] [PMC free article] [PubMed] [Google Scholar]
[162].Pan X, Chen S, Shen R, et al. Hoxa11-OS participates in lupus nephritis by targeting miR-124-3p mediating Cyr61 to regulate podocyte autophagy. Mol Med. 2022;28(1):138. doi: 10.1186/s10020-022-00570-w [DOI] [PMC free article] [PubMed] [Google Scholar]
[163].Yildirim D, Bender O, Karagoz ZF, et al. Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis. Life Sci. 2021;280(119671):119671. doi: 10.1016/j.lfs.2021.119671 [DOI] [PubMed] [Google Scholar]
[164].Liu Z, Yang D, Gao J, et al. Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis. Theranostics. 2020;10(26):11963–11975. doi: 10.7150/thno.50093 [DOI] [PMC free article] [PubMed] [Google Scholar]
[165].Chen G, Liu B, Chen S, et al. Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles. Int J Biol Sci. 2021;17(3):882–896. doi: 10.7150/ijbs.45294 [DOI] [PMC free article] [PubMed] [Google Scholar]
[166].Peng X, Li H, Zhang W, et al. Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury. Cell Mol Life Sci. 2024;81(1):154. doi: 10.1007/s00018-023-05079-x [DOI] [PMC free article] [PubMed] [Google Scholar]
[167].Lee EC, Valencia T, Allerson C, et al. Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Nat Commun. 2019;10(1):4148. doi: 10.1038/s41467-019-11918-y [DOI] [PMC free article] [PubMed] [Google Scholar]
[168].Qu L, Ding J, Chen C, et al. Exosome-transmitted lncarSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell. 2016;29(5):653–668. doi: 10.1016/j.ccell.2016.03.004 [DOI] [PubMed] [Google Scholar]
[169].Wang Y, Yang T, Li Q, et al. CircASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4. Mol Cancer. 2025;24(1):1. doi: 10.1186/s12943-024-02122-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
[170].Mahtal N, Lenoir O, Tinel C, et al. MicroRNAs in kidney injury and disease. Nat Rev Nephrol. 2022;18(10):643–662. doi: 10.1038/s41581-022-00608-6 [DOI] [PubMed] [Google Scholar]
[171].Flippot R, Beinse G, Boileve A, et al. Long non-coding RNAs in genitourinary malignancies: a whole new world. Nat Rev Urol. 2019;16(8):484–504. doi: 10.1038/s41585-019-0195-1 [DOI] [PubMed] [Google Scholar]
[172].van Zonneveld AJ, Kolling M, Bijkerk R, et al. Circular RNAs in kidney disease and cancer. Nat Rev Nephrol. 2021;17(12):814–826. doi: 10.1038/s41581-021-00465-9 [DOI] [PubMed] [Google Scholar]
[173].Butz H, Patocs A, Igaz P. Circulating non-coding RNA biomarkers of endocrine tumours. Nat Rev Endocrinol. 2024;20(10):600–614. doi: 10.1038/s41574-024-01005-8 [DOI] [PubMed] [Google Scholar]
[174].Liu Z, Fu Y, Yan M, et al. MicroRNAs in kidney diseases: regulation, therapeutics, and biomarker potential. Pharmacol Ther. 2024;262(108709):108709. doi: 10.1016/j.pharmthera.2024.108709 [DOI] [PubMed] [Google Scholar]
[175].Chiba T, Cerqueira DM, Li Y, et al. Endothelial-derived miR-17 approximately 92 promotes angiogenesis to protect against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2021;32(3):553–562. doi: 10.1681/ASN.2020050717 [DOI] [PMC free article] [PubMed] [Google Scholar]
[176].Zhao B, Li H, Liu J, et al. MicroRNA-23b targets ras GTPase-activating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy. J Am Soc Nephrol. 2016;27(9):2597–2608. doi: 10.1681/ASN.2015030300 [DOI] [PMC free article] [PubMed] [Google Scholar]
[177].Wang P, Huang Z, Peng Y, et al. Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair. Nat Commun. 2022;13(1):6502. doi: 10.1038/s41467-022-34287-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
[178].Kolling M, Seeger H, Haddad G, et al. The circular RNA ciRs-126 predicts survival in critically ill patients with acute kidney injury. Kidney Int Rep. 2018;3(5):1144–1152. doi: 10.1016/j.ekir.2018.05.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
[179].Bai S, Xiong X, Tang B, et al. Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-kappaB/MMP-2 axis. Cell Death Dis. 2020;11(11):1008. doi: 10.1038/s41419-020-03169-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
[180].Satake E, Saulnier PJ, Kobayashi H, et al. Comprehensive search for novel circulating miRNAs and axon guidance pathway proteins associated with risk of ESKD in diabetes. J Am Soc Nephrol. 2021;32(9):2331–2351. doi: 10.1681/ASN.2021010105 [DOI] [PMC free article] [PubMed] [Google Scholar]
[181].Lorenzen JM, Schauerte C, Kielstein JT, et al. Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury. Clin Chem. 2015;61(1):191–201. doi: 10.1373/clinchem.2014.230359 [DOI] [PubMed] [Google Scholar]
[182].Mao W, Wang K, Xu B, et al. Cirs-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma. Mol Cancer. 2021;20(1):142. doi: 10.1186/s12943-021-01443-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
[183].Wen JH, Li DY, Liang S, et al. Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis. Front Immunol. 2022;13(946832). doi: 10.3389/fimmu.2022.946832 [DOI] [PMC free article] [PubMed] [Google Scholar]
[184].Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 2020;16(9):489–508. doi: 10.1038/s41581-020-0309-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
[185].Liang S, Wu YS, Li DY, et al. Autophagy and renal fibrosis. Aging Dis. 2022;13(3):712–731. doi: 10.14336/AD.2021.1027 [DOI] [PMC free article] [PubMed] [Google Scholar]
[186].Guo L, Tan K, Luo Q, et al. Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy. Bosn J Basic Med Sci. 2020;20(3):372–380. doi: 10.17305/bjbms.2019.4410 [DOI] [PMC free article] [PubMed] [Google Scholar]
[187].Williams RM, Jaimes EA, Heller DA. Nanomedicines for kidney diseases. Kidney Int. 2016;90(4):740–745. doi: 10.1016/j.kint.2016.03.041 [DOI] [PMC free article] [PubMed] [Google Scholar]
[188].Tsai YC, Teng IL, Jiang ST, et al. Safe nanocomposite-mediated efficient delivery of MicroRNA plasmids for autosomal dominant polycystic kidney disease (ADPKD) therapy. Adv Healthc Mater. 2019;8(5):e1801358. doi: 10.1002/adhm.201801358 [DOI] [PubMed] [Google Scholar]
[189].Al-Tantawy SM, Eraky SM, Eissa LA. Promising renoprotective effect of gold nanoparticles and dapagliflozin in diabetic nephropathy via targeting miR-192 and miR-21. J Biochem Mol Toxicol. 2023;37(10):e23430. doi: 10.1002/jbt.23430 [DOI] [PubMed] [Google Scholar]
[190].Morishita Y, Imai T, Yoshizawa H, et al. Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo. Int J Nanomedicine. 2015;10(3475–88):3475. doi: 10.2147/IJN.S82587 [DOI] [PMC free article] [PubMed] [Google Scholar]
[191].Zhang Y, Li Y, Lin C, et al. Dioscin-loaded zein nanoparticles alleviate lipopolysaccharide-induced acute kidney injury via the microRNA-let 7i signalling pathways. IET Nanobiotechnol. 2021;15(5):465–472. doi: 10.1049/nbt2.12051 [DOI] [PMC free article] [PubMed] [Google Scholar]
[192].Gootenberg JS, Abudayyeh OO, Kellner MJ, et al. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science. 2018;360(6387):439–444. doi: 10.1126/science.aaq0179 [DOI] [PMC free article] [PubMed] [Google Scholar]
[193].Broto M, Kaminski MM, Adrianus C, et al. Nanozyme-catalysed CRISPR assay for preamplification-free detection of non-coding RNAs. Nat Nanotechnol. 2022;17(10):1120–1126. doi: 10.1038/s41565-022-01179-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
[194].Li S, Wu H, Chen LL. Screening circular RNAs with functional potential using the RfxCas13d/BSJ-gRNA system. Nat Protoc. 2022;17(9):2085–2107. doi: 10.1038/s41596-022-00715-5 [DOI] [PubMed] [Google Scholar]
[195].Wang W, Zhang M, Ren X, et al. Single-cell dissection of cellular and molecular features underlying mesenchymal stem cell therapy in ischemic acute kidney injury. Mol Ther. 2023;31(10):3067–3083. doi: 10.1016/j.ymthe.2023.07.024 [DOI] [PMC free article] [PubMed] [Google Scholar]
[196].Fan X, Zhang X, Wu X, et al. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol. 2015;16(1):148. doi: 10.1186/s13059-015-0706-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
[197].Jones D. Setbacks shadow microRNA therapies in the clinic. Nat Biotechnol. 2018;36(10):909–910. doi: 10.1038/nbt1018-909 [DOI] [PubMed] [Google Scholar]
[198].Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–222. doi: 10.1038/nrd.2016.246 [DOI] [PubMed] [Google Scholar]
[199].He AT, Liu J, Li F, et al. Targeting circular RNAs as a therapeutic approach: current strategies and challenges. Signal Transduct Target Ther. 2021;6(1):185. doi: 10.1038/s41392-021-00569-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
[200].Xia S, Feng J, Lei L, et al. Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform. 2017;18(6):984–992. doi: 10.1093/bib/bbw081 [DOI] [PubMed] [Google Scholar]
[201].Zhao Q, Liu J, Deng H, et al. Targeting mitochondria-located circRNA SCAR alleviates NASH via reducing mROS output. Cell. 2020;183(1):76–93 e22. doi: 10.1016/j.cell.2020.08.009 [DOI] [PubMed] [Google Scholar]
[202].Yi Z, Zhao Y, Yi Z, et al. Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice. Genome Biol. 2023;24(1):243. doi: 10.1186/s13059-023-03086-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
[203].Fan L, Yao L, Li Z, et al. Exosome-based mitochondrial delivery of circRNA mSCAR alleviates sepsis by orchestrating macrophage activation. Adv Sci (Weinh). 2023;10(14):e2205692. doi: 10.1002/advs.202205692 [DOI] [PMC free article] [PubMed] [Google Scholar]
[204].Wu N, Qadir J, Yang BB. CircRNA perspective: new strategies for RNA therapy. Trends Mol Med. 2022;28(4):343–344. doi: 10.1016/j.molmed.2022.02.002 [DOI] [PubMed] [Google Scholar]
[205].Fromm B, Zhong X, Tarbier M, et al. The limits of human microRNA annotation have been met. RNA. 2022;28(6):781–785. doi: 10.1261/rna.079098.122 [DOI] [PMC free article] [PubMed] [Google Scholar]
[206].Guo J, Yang Z, Yang X, et al. MiR-346 functions as a pro-survival factor under ER stress by activating mitophagy. Cancer Lett. 2018;413(69):69–81. doi: 10.1016/j.canlet.2017.10.030 [DOI] [PubMed] [Google Scholar]
[207].Wang Y, Liu T, Wu Y, et al. Lipid homeostasis in diabetic kidney disease. Int J Biol Sci. 2024;20(10):3710–3724. doi: 10.7150/ijbs.95216 [DOI] [PMC free article] [PubMed] [Google Scholar]
[208].Bhatia D, Choi ME. Autophagy and mitophagy: physiological implications in kidney inflammation and diseases. Am J Physiol Renal Physiol. 2023;325(1):F1–F21. doi: 10.1152/ajprenal.00012.2023 [DOI] [PMC free article] [PubMed] [Google Scholar]
[209].Kaushal GP, Chandrashekar K, Juncos LA. Molecular interactions between reactive oxygen species and autophagy in kidney disease. Int J Mol Sci. 2019;20(15):3791. doi: 10.3390/ijms20153791 [DOI] [PMC free article] [PubMed] [Google Scholar]
[210].Zhao H, Yang M, Han Y, et al. HIF-1alpha/BNIP3-mediated endoplasmic reticulum degradation via autophagy protects against ischemia reperfusion-induced acute kidney injury. Antioxid Redox Signal. 2025;42(4–6):212–227. doi: 10.1089/ars.2023.0467 [DOI] [PubMed] [Google Scholar]
[211].Morleo M, Brillante S, Formisano U, et al. Regulation of autophagosome biogenesis by OFD1-mediated selective autophagy. Embo J. 2021;40(4):e105120. doi: 10.15252/embj.2020105120 [DOI] [PMC free article] [PubMed] [Google Scholar]
[212].Sureshbabu A, Ryter SW, Choi ME. Oxidative stress and autophagy: crucial modulators of kidney injury. Redox Biol. 2015;4(208):208–214. doi: 10.1016/j.redox.2015.01.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
[213].Livingston MJ, Ding HF, Huang S, et al. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy. 2016;12(6):976–998. doi: 10.1080/15548627.2016.1166317 [DOI] [PMC free article] [PubMed] [Google Scholar]
[214].Li Z, Hao S, Yin H, et al. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice. Behav Brain Res. 2016;305(265):265–277. doi: 10.1016/j.bbr.2016.03.023 [DOI] [PubMed] [Google Scholar]

[cit0001] [1].Francis A, Harhay MN, Ong ACM, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. 2024;20(7):473–485. doi: 10.1038/s41581-024-00820-6 [DOI] [PubMed] [Google Scholar]

[cit0002] [2].Taylor SD. Bibliography on nursing research, 1950–1974. Nurs Res. 1975;24(3):207–225. doi: 10.1097/00006199-197505000-00015 [DOI] [PubMed] [Google Scholar]

[cit0003] [3].Leibovich BC, Lohse CM, Crispen PL, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 2010;183(4):1309–1315. doi: 10.1016/j.juro.2009.12.035 [DOI] [PubMed] [Google Scholar]

[cit0004] [4].Lipworth L, Morgans AK, Edwards TL, et al. Renal cell cancer histological subtype distribution differs by race and sex. BJU Int. 2016;117(2):260–265. doi: 10.1111/bju.12950 [DOI] [PubMed] [Google Scholar]

[cit0005] [5].Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet. 2015;385(9981):1975–1982. doi: 10.1016/S0140-6736(14)61601-9 [DOI] [PubMed] [Google Scholar]

[cit0006] [6].Liu WJ, Luo MN, Tan J, et al. Autophagy activation reduces renal tubular injury induced by urinary proteins. Autophagy. 2014;10(2):243–256. doi: 10.4161/auto.27004 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0007] [7].Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379(9811):165–180. doi: 10.1016/S0140-6736(11)60178-5 [DOI] [PubMed] [Google Scholar]

[cit0008] [8].Huang XR, Ye L, An N, et al. Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1. Autophagy. 2025;21(1):120–140. doi: 10.1080/15548627.2024.2393926 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0009] [9].Kimura T, Isaka Y, Yoshimori T. Autophagy and kidney inflammation. Autophagy. 2017;13(6):997–1003. doi: 10.1080/15548627.2017.1309485 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0010] [10].Su L, Zhang J, Gomez H, et al. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2023;19(2):401–414. doi: 10.1080/15548627.2022.2084862 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0011] [11].Minami S, Sakai S, Yamamoto T, et al. Fgf21 and autophagy coordinately counteract kidney disease progression during aging and obesity. Autophagy. 2024;20(3):489–504. doi: 10.1080/15548627.2023.2259282 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0012] [12].Deng Z, He M, Hu H, et al. Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation. Autophagy. 2024;20(1):151–165. doi: 10.1080/15548627.2023.2252265 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0013] [13].Livingston MJ, Shu S, Fan Y, et al. Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis. Autophagy. 2023;19(1):256–277. doi: 10.1080/15548627.2022.2072054 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0014] [14].Livingston MJ, Zhang M, Kwon SH, et al. Autophagy activates EGR1 via MAPK/ERK to induce FGF2 in renal tubular cells for fibroblast activation and fibrosis during maladaptive kidney repair. Autophagy. 2024;20(5):1032–1053. doi: 10.1080/15548627.2023.2281156 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0015] [15].Huynh C, Ryu J, Lee J, et al. Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases. Nat Rev Nephrol. 2023;19(2):102–122. doi: 10.1038/s41581-022-00648-y [DOI] [PubMed] [Google Scholar]

[cit0016] [16].Shi Y, Tao M, Ma X, et al. Delayed treatment with an autophagy inhibitor 3-MA alleviates the progression of hyperuricemic nephropathy. Cell Death Dis. 2020;11(6):467. doi: 10.1038/s41419-020-2673-z [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0017] [17].Zhu H, Wu H, Liu X, et al. Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy. 2009;5(6):816–823. doi: 10.4161/auto.9064 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0018] [18].Wang P, Luo ML, Song E, et al. Long noncoding RNA lnc-TSI inhibits renal fibrogenesis by negatively regulating the TGF-beta/Smad3 pathway. Sci Transl Med. 2018;10(462). doi: 10.1126/scitranslmed.aat2039 [DOI] [PubMed] [Google Scholar]

[cit0019] [19].Ward M, McEwan C, Mills JD, et al. Conservation and tissue-specific transcription patterns of long noncoding RNAs. J Hum Transcriptome. 2015;1(1):2–9. doi: 10.3109/23324015.2015.1077591 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0020] [20].Ying L, Huang Y, Chen H, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–411. doi: 10.1039/c2mb25386k [DOI] [PubMed] [Google Scholar]

[cit0021] [21].Huang R, Zhang Y, Han B, et al. Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG. Autophagy. 2017;13(10):1722–1741. doi: 10.1080/15548627.2017.1356975 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0022] [22].Zhang P, Wu W, Chen Q, et al. Non-coding RNAs and their integrated networks. J Integr Bioinform. 2019;16(3). doi: 10.1515/jib-2019-0027 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0023] [23].Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–227. doi: 10.1038/nature07672 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0024] [24].Cabili MN, Trapnell C, Goff L, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915–1927. doi: 10.1101/gad.17446611 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0025] [25].Cerutti P, Holt JW, Miller N. Detection and determination of 5,6-dihydrouridine and 4-thiouridine in transfer ribonucleic acid from different sources. J Mol Biol. 1968;34(3):505–518. doi: 10.1016/0022-2836(68)90176-9 [DOI] [PubMed] [Google Scholar]

[cit0026] [26].Chen Q, Meng X, Liao Q, et al. Versatile interactions and bioinformatics analysis of noncoding RNAs. Brief Bioinform. 2019;20(5):1781–1794. doi: 10.1093/bib/bby050 [DOI] [PubMed] [Google Scholar]

[cit0027] [27].Hombach S, Kretz M. Non-coding RNAs: classification, biology and functioning. Adv Exp Med Biol. 2016;937(3–17). doi: 10.1007/978-3-319-42059-2_1 [DOI] [PubMed] [Google Scholar]

[cit0028] [28].Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–157. doi: 10.1261/rna.035667.112 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0029] [29].Farazi TA, Hoell JI, Morozov P, et al. MicroRNAs in human cancer. Adv Exp Med Biol. 2013;774(1–20). doi: 10.1007/978-94-007-5590-1_1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0030] [30].Bartel DP. Metazoan microRNAs. Cell. 2018;173(1):20–51. doi: 10.1016/j.cell.2018.03.006 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0031] [31].Wang P, Chen W, Zhao S, et al. The role of lncRNA-regulated autophagy in AKI. Biofactors. 2023;49(5):1010–1021. doi: 10.1002/biof.1980 [DOI] [PubMed] [Google Scholar]

[cit0032] [32].Sauvageau M. Diverging RNPs: toward understanding lncRNA-protein interactions and functions. Adv Exp Med Biol. 2019;1203(285–312). doi: 10.1007/978-3-030-31434-7_10 [DOI] [PubMed] [Google Scholar]

[cit0033] [33].Elguindy MM, Kopp F, Goodarzi M, et al. PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD. Elife. 2019;8. doi: 10.7554/eLife.48625 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0034] [34].Pandey PR, Rout PK, Das A, et al. Rpad (RNase R treatment, polyadenylation, and poly(A)+ RNA depletion) method to isolate highly pure circular RNA. Methods. 2019;155(41):41–48. doi: 10.1016/j.ymeth.2018.10.022 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0035] [35].Zhong Y, Du Y, Yang X, et al. Circular RNAs function as ceRnas to regulate and control human cancer progression. Mol Cancer. 2018;17(1):79. doi: 10.1186/s12943-018-0827-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0036] [36].Zhu P, Zhu X, Wu J, et al. Il-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat Immunol. 2019;20(2):183–194. doi: 10.1038/s41590-018-0297-6 [DOI] [PubMed] [Google Scholar]

[cit0037] [37].Chen Y, Yang F, Fang E, et al. Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes. Cell Death Differ. 2019;26(7):1346–1364. doi: 10.1038/s41418-018-0220-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0038] [38].Yang ZG, Awan FM, Du WW, et al. The circular RNA interacts with STAT3, increasing its nuclear translocation and wound repair by modulating Dnmt3a and miR-17 function. Mol Ther. 2017;25(9):2062–2074. doi: 10.1016/j.ymthe.2017.05.022 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0039] [39].Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66(1):22–37 e9. doi: 10.1016/j.molcel.2017.02.017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0040] [40].Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–131. doi: 10.1016/j.ceb.2009.11.014 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0041] [41].Mijaljica D, Prescott M, Devenish RJ. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy. 2011;7(7):673–682. doi: 10.4161/auto.7.7.14733 [DOI] [PubMed] [Google Scholar]

[cit0042] [42].Massey A, Kiffin R, Cuervo AM. Pathophysiology of chaperone-mediated autophagy. Int J Biochem Cell Biol. 2004;36(12):2420–2434. doi: 10.1016/j.biocel.2004.04.010 [DOI] [PubMed] [Google Scholar]

[cit0043] [43].Tekirdag K, Cuervo AM. Chaperone-mediated autophagy and endosomal microautophagy: joint by a chaperone. J Biol Chem. 2018;293(15):5414–5424. doi: 10.1074/jbc.R117.818237 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0044] [44].Vargas JNS, Hamasaki M, Kawabata T, et al. The mechanisms and roles of selective autophagy in mammals. Nat Rev Mol Cell Biol. 2023;24(3):167–185. doi: 10.1038/s41580-022-00542-2 [DOI] [PubMed] [Google Scholar]

[cit0045] [45].Lamark T, Johansen T. Mechanisms of selective autophagy. Annu Rev Cell Dev Biol. 2021;37(143–69):143–169. doi: 10.1146/annurev-cellbio-120219-035530 [DOI] [PubMed] [Google Scholar]

[cit0046] [46].Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol. 2009;335(1–32). doi: 10.1007/978-3-642-00302-8_1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0047] [47].Chiu HC, Richart S, Lin FY, et al. The interplay of reovirus with autophagy. Biomed Res Int. 2014;2014(483657):1–8. doi: 10.1155/2014/483657 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0048] [48].Sergin I, Razani B. Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis. Trends Endocrinol Metab. 2014;25(5):225–234. doi: 10.1016/j.tem.2014.03.010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0049] [49].Stead ER, Castillo-Quan JI, Miguel VEM, et al. Agephagy - adapting autophagy for health during aging. Front Cell Dev Biol. 2019;7(308). doi: 10.3389/fcell.2019.00308 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0050] [50].Jung CH, Ro SH, Cao J, et al. mTOR regulation of autophagy. FEBS Lett. 2010;584(7):1287–1295. doi: 10.1016/j.febslet.2010.01.017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0051] [51].Alers S, Loffler AS, Wesselborg S, et al. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol. 2012;32(1):2–11. doi: 10.1128/MCB.06159-11 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0052] [52].Tanida I, Ueno T, Kominami E. Lc3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503–2518. doi: 10.1016/j.biocel.2004.05.009 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0053] [53].Kim J, Kundu M, Viollet B, et al. Ampk and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132–141. doi: 10.1038/ncb2152 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0054] [54].Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280–293. doi: 10.1016/j.molcel.2010.09.023 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0055] [55].Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728–741. doi: 10.1016/j.cell.2011.10.026 [DOI] [PubMed] [Google Scholar]

[cit0056] [56].Maiuri MC, Le Toumelin G, Criollo A, et al. Functional and physical interaction between Bcl-x(L) and a BH3-like domain in Beclin-1. Embo J. 2007;26(10):2527–2539. doi: 10.1038/sj.emboj.7601689 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0057] [57].Carriere A, Romeo Y, Acosta-Jaquez HA, et al. Erk1/2 phosphorylate raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem. 2011;286(1):567–577. doi: 10.1074/jbc.M110.159046 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0058] [58].Kim JH, Hong SK, Wu PK, et al. Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels. Exp Cell Res. 2014;327(2):340–352. doi: 10.1016/j.yexcr.2014.08.001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0059] [59].He Y, She H, Zhang T, et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol. 2018;217(1):315–328. doi: 10.1083/jcb.201701049 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0060] [60].McClung JM, Judge AR, Powers SK, et al. p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol. 2010;298(3):C542–9. doi: 10.1152/ajpcell.00192.2009 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0061] [61].Lin R, Feng J, Dong S, et al. Regulation of autophagy of prostate cancer cells by beta-catenin signaling. Cell Physiol Biochem. 2015;35(3):926–932. doi: 10.1159/000369749 [DOI] [PubMed] [Google Scholar]

[cit0062] [62].Crighton D, Wilkinson S, O’Prey J, et al. Dram, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126(1):121–134. doi: 10.1016/j.cell.2006.05.034 [DOI] [PubMed] [Google Scholar]

[cit0063] [63].Jia J, Abudu YP, Claude-Taupin A, et al. Galectins control mTOR in response to endomembrane damage. Mol Cell. 2018;70(1):120–35 e8. doi: 10.1016/j.molcel.2018.03.009 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0064] [64].Lee IH, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105(9):3374–3379. doi: 10.1073/pnas.0712145105 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0065] [65].Keith B, Johnson RS, Simon MC. HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2011;12(1):9–22. doi: 10.1038/nrc3183 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0066] [66].White E, Mehnert JM, Autophagy CC. Metabolism, and cancer. Clin Cancer Res. 2015;21(22):5037–5046. doi: 10.1158/1078-0432.CCR-15-0490 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0067] [67].White E. The role for autophagy in cancer. J Clin Invest. 2015;125(1):42–46. doi: 10.1172/JCI73941 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0068] [68].Janku F, McConkey DJ, Hong DS, et al. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011;8(9):528–539. doi: 10.1038/nrclinonc.2011.71 [DOI] [PubMed] [Google Scholar]

[cit0069] [69].Cao Q, Bai P. Role of autophagy in renal cancer. J Cancer. 2019;10(11):2501–2509. doi: 10.7150/jca.29285 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0070] [70].Sun J, Ding J, Yue H, et al. Hypoxia-induced BNIP3 facilitates the progression and metastasis of uveal melanoma by driving metabolic reprogramming. Autophagy. 2025;21(1):191–209. doi: 10.1080/15548627.2024.2395142 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0071] [71].Murugesan T, Rajajeyabalachandran G, Kumar S, et al. Targeting HIF-2alpha as therapy for advanced cancers. Drug Discov Today. 2018;23(7):1444–1451. doi: 10.1016/j.drudis.2018.05.003 [DOI] [PubMed] [Google Scholar]

[cit0072] [72].Ferro F, Servais S, Besson P, et al. Autophagy and mitophagy in cancer metabolic remodelling. Semin Cell Dev Biol. 2020;98(129):129–138. doi: 10.1016/j.semcdb.2019.05.029 [DOI] [PubMed] [Google Scholar]

[cit0073] [73].Gao L, Chen Y. Autophagy controls programmed death-ligand 1 expression on cancer cells (review). Biomed Rep. 2021;15(4):84. doi: 10.3892/br.2021.1460 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0074] [74].Messai Y, Noman MZ, Hasmim M, et al. Itpr1 protects renal cancer cells against natural killer cells by inducing autophagy. Cancer Res. 2014;74(23):6820–6832. doi: 10.1158/0008-5472.CAN-14-0303 [DOI] [PubMed] [Google Scholar]

[cit0075] [75].Messai Y, Noman MZ, Janji B, et al. The autophagy sensor ITPR1 protects renal carcinoma cells from NK-mediated killing. Autophagy. 2015:0. doi: 10.1080/15548627.2015.1017194 [DOI] [PubMed] [Google Scholar]

[cit0076] [76].White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 2012;12(6):401–410. doi: 10.1038/nrc3262 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0077] [77].Chien CT, Shyue SK, Lai MK. Bcl-xL augmentation potentially reduces ischemia/reperfusion induced proximal and distal tubular apoptosis and autophagy. Transplantation. 2007;84(9):1183–1190. doi: 10.1097/01.tp.0000287334.38933.e3 [DOI] [PubMed] [Google Scholar]

[cit0078] [78].Suzuki C, Isaka Y, Takabatake Y, et al. Participation of autophagy in renal ischemia/reperfusion injury. Biochem Biophys Res Commun. 2008;368(1):100–106. doi: 10.1016/j.bbrc.2008.01.059 [DOI] [PubMed] [Google Scholar]

[cit0079] [79].Tang C, Han H, Yan M, et al. Pink1-Prkn/Park2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury. Autophagy. 2018;14(5):880–897. doi: 10.1080/15548627.2017.1405880 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0080] [80].He L, Livingston MJ, Dong Z. Autophagy in acute kidney injury and repair. Nephron Clin Pract. 2014;127(1–4):56–60. doi: 10.1159/000363677 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0081] [81].Jiang M, Liu K, Luo J, et al. Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. Am J Pathol. 2010;176(3):1181–1192. doi: 10.2353/ajpath.2010.090594 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0082] [82].Leventhal JS, Ni J, Osmond M, et al. Autophagy limits endotoxemic acute kidney injury and alters renal tubular epithelial cell cytokine expression. PLOS ONE. 2016;11(3):e0150001. doi: 10.1371/journal.pone.0150001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0083] [83].Mei S, Livingston M, Hao J, et al. Autophagy is activated to protect against endotoxic acute kidney injury. Sci Rep. 2016;6(22171). doi: 10.1038/srep22171 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0084] [84].Wu Y, Zhang Y, Wang L, et al. The role of autophagy in kidney inflammatory injury via the NF-kappaB route induced by LPS. Int J Med Sci. 2015;12(8):655–667. doi: 10.7150/ijms.12460 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0085] [85].Takahashi W, Watanabe E, Fujimura L, et al. Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. Crit Care. 2013;17(4):R160. doi: 10.1186/cc12839 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0086] [86].Sunahara S, Watanabe E, Hatano M, et al. Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model. Sci Rep. 2018;8(1):1050. doi: 10.1038/s41598-018-19350-w [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0087] [87].Periyasamy-Thandavan S, Jiang M, Wei Q, et al. Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. Kidney Int. 2008;74(5):631–640. doi: 10.1038/ki.2008.214 [DOI] [PubMed] [Google Scholar]

[cit0088] [88].Lee SY, Kim SI, Choi ME. Therapeutic targets for treating fibrotic kidney diseases. Transl Res. 2015;165(4):512–530. doi: 10.1016/j.trsl.2014.07.010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0089] [89].Ammirati AL. Chronic kidney disease. Rev Assoc Med Bras. 2020;66(Suppl 1):s03–s9. doi: 10.1590/1806-9282.66.S1.3 [DOI] [PubMed] [Google Scholar]

[cit0090] [90].Liu N, Shi Y, Zhuang S. Autophagy in chronic kidney diseases. Kidney Dis (Basel). 2016;2(1):37–45. doi: 10.1159/000444841 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0091] [91].Lin TA, Wu VC, Wang CY. Autophagy in chronic kidney diseases. Cells. 2019;8(1):61. doi: 10.3390/cells8010061 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0092] [92].De Rechter S, Decuypere JP, Ivanova E, et al. Autophagy in renal diseases. Pediatr Nephrol. 2016;31(5):737–752. doi: 10.1007/s00467-015-3134-2 [DOI] [PubMed] [Google Scholar]

[cit0093] [93].Koch EAT, Nakhoul R, Nakhoul F, et al. Autophagy in diabetic nephropathy: a review. Int Urol Nephrol. 2020;52(9):1705–1712. doi: 10.1007/s11255-020-02545-4 [DOI] [PubMed] [Google Scholar]

[cit0094] [94].Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2016;12(2):73–81. doi: 10.1038/nrneph.2015.173 [DOI] [PubMed] [Google Scholar]

[cit0095] [95].Nam SA, Kim WY, Kim JW, et al. Autophagy attenuates tubulointerstitial fibrosis through regulating transforming growth factor-beta and NLRP3 inflammasome signaling pathway. Cell Death Dis. 2019;10(2):78. doi: 10.1038/s41419-019-1356-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0096] [96].Belibi F, Zafar I, Ravichandran K, et al. Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD). Am J Physiol Renal Physiol. 2011;300(5):F1235–43. doi: 10.1152/ajprenal.00348.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0097] [97].Zafar I, Ravichandran K, Belibi FA, et al. Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease. Kidney Int. 2010;78(8):754–761. doi: 10.1038/ki.2010.250 [DOI] [PubMed] [Google Scholar]

[cit0098] [98].Zhu P, Sieben CJ, Xu X, et al. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Hum Mol Genet. 2017;26(1):158–172. doi: 10.1093/hmg/ddw376 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0099] [99].Mikhaylova O, Stratton Y, Hall D, et al. VHL-regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 2012;21(4):532–546. doi: 10.1016/j.ccr.2012.02.019 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0100] [100].Hall DP, Cost NG, Hegde S, et al. Trpm3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma. Cancer Cell. 2014;26(5):738–753. doi: 10.1016/j.ccell.2014.09.015 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0101] [101].Zheng B, Zhu H, Gu D, et al. miRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib. Biochem Biophys Res Commun. 2015;459(2):234–239. doi: 10.1016/j.bbrc.2015.02.084 [DOI] [PubMed] [Google Scholar]

[cit0102] [102].Long JS, Ryan KM. New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy. Oncogene. 2012;31(49):5045–5060. doi: 10.1038/onc.2012.7 [DOI] [PubMed] [Google Scholar]

[cit0103] [103].Gao C, Peng FH, Peng LK. MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1. Neoplasma. 2014;61(6):680–689. doi: 10.4149/neo_2014_083 [DOI] [PubMed] [Google Scholar]

[cit0104] [104].Patergnani S, Guzzo S, Mangolini A, et al. The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells. Exp Cell Res. 2020;395(1):112190. doi: 10.1016/j.yexcr.2020.112190 [DOI] [PubMed] [Google Scholar]

[cit0105] [105].Su Y, Lu J, Chen X, et al. Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway. J Cancer Res Clin Oncol. 2019;145(3):573–588. doi: 10.1007/s00432-018-2808-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0106] [106].Wang B, Wei Y, Han T, et al. LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy. Eur J Med Res. 2024;29(1):103. doi: 10.1186/s40001-024-01690-1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0107] [107].Pan Y, Lu X, Shu G, et al. Extracellular vesicle-mediated transfer of lncRNA IGFL2-AS1 confers sunitinib resistance in renal cell carcinoma. Cancer Res. 2023;83(1):103–116. doi: 10.1158/0008-5472.CAN-21-3432 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0108] [108].Yang X, Zhang Y, Fan H. Downregulation of SBF2-AS1 functions as a tumor suppressor in clear cell renal cell carcinoma by inhibiting miR-338-3p-targeted ETS1. Cancer Gene Ther. 2021;28(7–8):813–827. doi: 10.1038/s41417-020-0197-4 [DOI] [PubMed] [Google Scholar]

[cit0109] [109].Jin Y, Huang R, Xia Y, et al. Long noncoding RNA KIF9-AS1 regulates transforming growth factor-beta and autophagy signaling to enhance renal cell carcinoma chemoresistance via microRNA-497-5p. DNA Cell Biol. 2020;39(7):1096–1103. doi: 10.1089/dna.2020.5453 [DOI] [PubMed] [Google Scholar]

[cit0110] [110].Li R, Luo S, Zhang D. Circular RNA hsa_circ_0054537 sponges miR-130a-3p to promote the progression of renal cell carcinoma through regulating cMet pathway. Gene. 2020;754(144811):144811. doi: 10.1016/j.gene.2020.144811 [DOI] [PubMed] [Google Scholar]

[cit0111] [111].Pei L, Lv X, Jia G, et al. Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2). Bioengineered. 2021;12(1):8279–8295. doi: 10.1080/21655979.2021.1984002 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0112] [112].Yan L, Liu G, Cao H, et al. Hsa_circ_0035483 sponges hsa-miR-335 to promote the gemcitabine-resistance of human renal cancer cells by autophagy regulation. Biochem Biophys Res Commun. 2019;519(1):172–178. doi: 10.1016/j.bbrc.2019.08.093 [DOI] [PubMed] [Google Scholar]

[cit0113] [113].Xu B, Yuan CW, Zhang JE. Curcumin inhibits proliferation of renal cell carcinoma in vitro and in vivo by regulating miR-148/ADAMTS18 through suppressing autophagy. Chin J Integr Med. 2023;29(8):699–706. doi: 10.1007/s11655-022-3690-9 [DOI] [PubMed] [Google Scholar]

[cit0114] [114].Liu X, Hong Q, Wang Z, et al. MiR-21 inhibits autophagy by targeting Rab11a in renal ischemia/reperfusion. Exp Cell Res. 2015;338(1):64–69. doi: 10.1016/j.yexcr.2015.08.010 [DOI] [PubMed] [Google Scholar]

[cit0115] [115].Wang IK, Sun KT, Tsai TH, et al. MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury. Life Sci. 2015;136(133):133–141. doi: 10.1016/j.lfs.2015.07.002 [DOI] [PubMed] [Google Scholar]

[cit0116] [116].Shao X, Zhang S, Tang Y, et al. Micro RNA-30b (inhibitor) nanoparticles suppressed the lipopolysaccharide (LPS)-induced acute kidney injury. IET Nanobiotechnol. 2019;13(9):923–927. doi: 10.1049/iet-nbt.2019.0110 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0117] [117].Liu XJ, Hong Q, Wang Z, et al. MicroRNA-34a suppresses autophagy in tubular epithelial cells in acute kidney injury. Am J Nephrol. 2015;42(2):168–175. doi: 10.1159/000439185 [DOI] [PubMed] [Google Scholar]

[cit0118] [118].Liu X, Li Q, Sun L, et al. miR-30e-5p regulates autophagy and apoptosis by targeting Beclin1 involved in contrast-induced acute kidney injury. Curr Med Chem. 2021;28(38):7974–7984. doi: 10.2174/0929867328666210526125023 [DOI] [PubMed] [Google Scholar]

[cit0119] [119].Zhao P, Zhu Y, Sun L, et al. Circulating exosomal miR-1-3p from rats with myocardial infarction plays a protective effect on contrast-induced nephropathy via targeting ATG13 and activating the AKT signaling pathway. Int J Biol Sci. 2021;17(4):972–985. doi: 10.7150/ijbs.55887 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0120] [120].Liu Y, Xiao J, Sun J, et al. Atg7 promotes autophagy in sepsis‑induced acute kidney injury and is inhibited by miR‑526b. Mol Med Rep. 2020;21(5):2193–2201. doi: 10.3892/mmr.2020.11001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0121] [121].Ma M, Li H, Yin S, et al. Overexpression of miR-92a attenuates kidney ischemia-reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy. Cell Mol Biol Lett. 2023;28(1):20. doi: 10.1186/s11658-023-00430-3 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0122] [122].Chen Y, Zhang C, Du Y, et al. Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6. Chin Med J (Engl). 2022;135(20):2467–2477. doi: 10.1097/CM9.0000000000002377 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0123] [123].Dong Y, Han X, Yang Y, et al. miR-506-3p induces autophagy of renal tubular epithelial cells in sepsis through targeting PI3K pathway. Aging (Albany NY). 2023;15(11):4734–4745. doi: 10.18632/aging.204759 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0124] [124].Wu T, Zhu W, Duan R, et al. Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p. J Nanobiotechnology. 2024;22(1):666. doi: 10.1186/s12951-024-02928-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0125] [125].Xiang J, Jiang T, Zhang W, et al. Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy through microRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Cell Res. 2019;378(2):198–205. doi: 10.1016/j.yexcr.2019.03.019 [DOI] [PubMed] [Google Scholar]

[cit0126] [126].Wang IK, Palanisamy K, Sun KT, et al. The functional interplay of lncRNA EGOT and HuR regulates hypoxia-induced autophagy in renal tubular cells. J Cell Biochem. 2020;121(11):4522–4534. doi: 10.1002/jcb.29669 [DOI] [PubMed] [Google Scholar]

[cit0127] [127].Ouyang X, He Z, Fang H, et al. A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway. Mol Ther. 2023;31(6):1722–1738. doi: 10.1016/j.ymthe.2022.09.007 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0128] [128].Yang N, Wang H, Zhang L, et al. Long non-coding RNA SNHG14 aggravates LPS-induced acute kidney injury through regulating miR-495-3p/HIPK1. Acta Biochim Biophys Sin (Shanghai). 2021;53(6):719–728. doi: 10.1093/abbs/gmab034 [DOI] [PubMed] [Google Scholar]

[cit0129] [129].Zhao W, Zhang Y, Zhang M, et al. Effects of total glucosides of paeony on acute renal injury following ischemia-reperfusion via the lncRNA HCG18/miR-16-5p/Bcl-2 axis. Immunobiology. 2022;227(2):152179. doi: 10.1016/j.imbio.2022.152179 [DOI] [PubMed] [Google Scholar]

[cit0130] [130].Chang X, Zhang P, Xu XX, et al. Total glucosides of paeony inhibited autophagy and improved acute kidney injury induced by ischemia-reperfusion via the lncRNA TUG1/miR-29a/PTEN axis. Drug Des Devel Ther. 2021;15(2229):2229–2242. doi: 10.2147/DDDT.S286606 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0131] [131].Han D, Fang R, Shi R, et al. LncRNA NKILA knockdown promotes cell viability and represses cell apoptosis, autophagy and inflammation in lipopolysaccharide-induced sepsis model by regulating miR-140-5p/CLDN2 axis. Biochem Biophys Res Commun. 2021;559(8):8–14. doi: 10.1016/j.bbrc.2021.04.074 [DOI] [PubMed] [Google Scholar]

[cit0132] [132].Liu D, Liu Y, Zheng X, et al. c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia-reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/beta-catenin pathway. Cell Death Dis. 2021;12(2):191. doi: 10.1038/s41419-021-03466-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0133] [133].Ma Z, Li L, Livingston MJ, et al. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. J Clin Invest. 2020;130(9):5011–5026. doi: 10.1172/JCI135536 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0134] [134].Zhang Y, Zhao S, Wu D, et al. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy. J Diabetes Res. 2018;2018(4728645):1–11. doi: 10.1155/2018/4728645 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0135] [135].Zhuang L, Ge X, Hu X, et al. MiR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8. BMC Nephrol. 2022;23(1):89. doi: 10.1186/s12882-022-02716-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0136] [136].Kato M, Abdollahi M, Tunduguru R, et al. MiR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1. Commun Biol. 2021;4(1):30. doi: 10.1038/s42003-020-01516-w [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0137] [137].Liu Y, Dong ZJ, Song JW, et al. MicroRNA-122-5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3. Exp Cell Res. 2022;411(2):113017. doi: 10.1016/j.yexcr.2022.113017 [DOI] [PubMed] [Google Scholar]

[cit0138] [138].Yang S, Abdulla R, Lu C, et al. Inhibition of microRNA-376b protects against renal interstitial fibrosis via inducing macrophage autophagy by upregulating Atg5 in mice with chronic kidney disease. Kidney Blood Press Res. 2018;43(6):1749–1764. doi: 10.1159/000495394 [DOI] [PubMed] [Google Scholar]

[cit0139] [139].Jianbing H, Xiaotian L, Jie T, et al. The effect of allograft inflammatory factor-1 on inflammation, oxidative stress, and autophagy via miR-34a/ATG4B pathway in diabetic kidney disease. Oxid Med Cell Longev. 2022;2022(1668000). doi: 10.1155/2022/1668000 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0140] [140].Cai X, Zou F, Xuan R, et al. Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy via the tumour necrosis factor receptor-associated factor 6/Akt axis. Endocr J. 2021;68(7):817–828. doi: 10.1507/endocrj.EJ20-0619 [DOI] [PubMed] [Google Scholar]

[cit0141] [141].Huang H, Liu H, Tang J, et al. M2 macrophage-derived exosomal miR-25-3p improves high glucose-induced podocytes injury through activation autophagy via inhibiting DUSP1 expression. IUBMB Life. 2020;72(12):2651–2662. doi: 10.1002/iub.2393 [DOI] [PubMed] [Google Scholar]

[cit0142] [142].Fan WX, Wen XL, Xiao H, et al. MicroRNA-29a enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis by targeting heme oxygenase-1. Eur Rev Med Pharmacol Sci. 2018;22(24):8909–8917. doi: 10.26355/eurrev_201812_16660 [DOI] [PubMed] [Google Scholar]

[cit0143] [143].Yoon YM, Go G, Yoon S, et al. Melatonin treatment improves renal fibrosis via miR-4516/SIAH3/PINK1 axis. Cells. 2021;10(7):1682. doi: 10.3390/cells10071682 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0144] [144].Su PP, Liu DW, Zhou SJ, et al. Down-regulation of RISA improves podocyte injury by enhancing autophagy in diabetic nephropathy. Mil Med Res. 2022;9(1):23. doi: 10.1186/s40779-022-00385-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0145] [145].Huang Y, Huang Y, Zhou Y, et al. Shensu IV prevents glomerular podocyte injury in nephrotic rats via promoting lncRNA H19/DIRAS3-mediated autophagy. Biosci Rep. 2021;41(5). doi: 10.1042/BSR20203362 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0146] [146].Guo F, Wang W, Song Y, et al. LncRNA SNHG17 knockdown promotes parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1. Cell Cycle. 2020;19(16):1997–2006. doi: 10.1080/15384101.2020.1783481 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0147] [147].Qi C, Liang T, Lin J, et al. Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells. Biochem Biophys Res Commun. 2023;644(95):95–104. doi: 10.1016/j.bbrc.2023.01.013 [DOI] [PubMed] [Google Scholar]

[cit0148] [148].Jin J, Gong J, Zhao L, et al. LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway. Acta Biochim Pol. 2021;68(4):619–625. doi: 10.18388/abp.2020_5483 [DOI] [PubMed] [Google Scholar]

[cit0149] [149].Yang N, Zhang Y, Ren P, et al. LncRNA AA465934 improves podocyte injury by promoting tristetraprolin-mediated HMGB1 downregulation in diabetic nephropathy. Mol Cell Biol. 2024;44(3):87–102. doi: 10.1080/10985549.2024.2325527 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0150] [150].Cai Y, Chen S, Jiang X, et al. LncRNA X inactive specific transcript exerts a protective effect on high glucose-induced podocytes by promoting the podocyte autophagy via miR-30d-5p/BECN-1 axis. Int J Endocrinol. 2023;2023(3187846):1–12. doi: 10.1155/2023/3187846 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0151] [151].Zhang Y, Chang B, Zhang J, et al. LncRNA SOX2OT alleviates the high glucose-induced podocytes injury through autophagy induction by the miR-9/SIRT1 axis. Exp Mol Pathol. 2019;110(104283):104283. doi: 10.1016/j.yexmp.2019.104283 [DOI] [PubMed] [Google Scholar]

[cit0152] [152].Liu X, Jiang L, Zeng H, et al. Circ-0000953 deficiency exacerbates podocyte injury and autophagy disorder by targeting Mir665-3p-Atg4b in diabetic nephropathy. Autophagy. 2024;20(5):1072–1097. doi: 10.1080/15548627.2023.2286128 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0153] [153].Wang Y, Zheng ZJ, Jia YJ, et al. Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease. J Transl Med. 2018;16(1):146. doi: 10.1186/s12967-018-1486-7 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0154] [154].Wang J, Shen L, Hong H, et al. Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis. Eur J Pharmacol. 2019;852(142):142–150. doi: 10.1016/j.ejphar.2019.03.013 [DOI] [PubMed] [Google Scholar]

[cit0155] [155].Liang Y, Liu H, Zhu J, et al. Inhibition of p53/miR-34a/SIRT1 axis ameliorates podocyte injury in diabetic nephropathy. Biochem Biophys Res Commun. 2021;559(48):48–55. doi: 10.1016/j.bbrc.2021.04.025 [DOI] [PubMed] [Google Scholar]

[cit0156] [156].Feng Y, Chen S, Xu J, et al. Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy. Mol Med Rep. 2018;18(4):3657–3664. doi: 10.3892/mmr.2018.9412 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0157] [157].Chen K, Yu B, Liao J. Lncrna sox2ot alleviates mesangial cell proliferation and fibrosis in diabetic nephropathy via akt/mTOR-mediated autophagy. Mol Med. 2021;27(1):71. doi: 10.1186/s10020-021-00310-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0158] [158].Xu J, Deng Y, Wang Y, et al. Spag5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell Prolif. 2020;53(2):e12738. doi: 10.1111/cpr.12738 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0159] [159].Chen X, Zhang XB, Li DJ, et al. MiR-155 facilitates calcium oxalate crystal-induced HK-2 cell injury via targeting PI3K associated autophagy. Exp Mol Pathol. 2020;115(104450):104450. doi: 10.1016/j.yexmp.2020.104450 [DOI] [PubMed] [Google Scholar]

[cit0160] [160].Shi J, Duan J, Gong H, et al. Exosomes from miR-20b-3p-overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney. J Cell Mol Med. 2019;23(11):7268–7278. doi: 10.1111/jcmm.14555 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0161] [161].Yu M, Shen X, He W, et al. Mesangial cell-derived exosomal miR-4455 induces podocyte injury in IgA nephropathy by targeting ULK2. Oxid Med Cell Longev. 2022;2022(1740770). doi: 10.1155/2022/1740770 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0162] [162].Pan X, Chen S, Shen R, et al. Hoxa11-OS participates in lupus nephritis by targeting miR-124-3p mediating Cyr61 to regulate podocyte autophagy. Mol Med. 2022;28(1):138. doi: 10.1186/s10020-022-00570-w [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0163] [163].Yildirim D, Bender O, Karagoz ZF, et al. Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis. Life Sci. 2021;280(119671):119671. doi: 10.1016/j.lfs.2021.119671 [DOI] [PubMed] [Google Scholar]

[cit0164] [164].Liu Z, Yang D, Gao J, et al. Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis. Theranostics. 2020;10(26):11963–11975. doi: 10.7150/thno.50093 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0165] [165].Chen G, Liu B, Chen S, et al. Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles. Int J Biol Sci. 2021;17(3):882–896. doi: 10.7150/ijbs.45294 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0166] [166].Peng X, Li H, Zhang W, et al. Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury. Cell Mol Life Sci. 2024;81(1):154. doi: 10.1007/s00018-023-05079-x [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0167] [167].Lee EC, Valencia T, Allerson C, et al. Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Nat Commun. 2019;10(1):4148. doi: 10.1038/s41467-019-11918-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0168] [168].Qu L, Ding J, Chen C, et al. Exosome-transmitted lncarSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell. 2016;29(5):653–668. doi: 10.1016/j.ccell.2016.03.004 [DOI] [PubMed] [Google Scholar]

[cit0169] [169].Wang Y, Yang T, Li Q, et al. CircASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4. Mol Cancer. 2025;24(1):1. doi: 10.1186/s12943-024-02122-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0170] [170].Mahtal N, Lenoir O, Tinel C, et al. MicroRNAs in kidney injury and disease. Nat Rev Nephrol. 2022;18(10):643–662. doi: 10.1038/s41581-022-00608-6 [DOI] [PubMed] [Google Scholar]

[cit0171] [171].Flippot R, Beinse G, Boileve A, et al. Long non-coding RNAs in genitourinary malignancies: a whole new world. Nat Rev Urol. 2019;16(8):484–504. doi: 10.1038/s41585-019-0195-1 [DOI] [PubMed] [Google Scholar]

[cit0172] [172].van Zonneveld AJ, Kolling M, Bijkerk R, et al. Circular RNAs in kidney disease and cancer. Nat Rev Nephrol. 2021;17(12):814–826. doi: 10.1038/s41581-021-00465-9 [DOI] [PubMed] [Google Scholar]

[cit0173] [173].Butz H, Patocs A, Igaz P. Circulating non-coding RNA biomarkers of endocrine tumours. Nat Rev Endocrinol. 2024;20(10):600–614. doi: 10.1038/s41574-024-01005-8 [DOI] [PubMed] [Google Scholar]

[cit0174] [174].Liu Z, Fu Y, Yan M, et al. MicroRNAs in kidney diseases: regulation, therapeutics, and biomarker potential. Pharmacol Ther. 2024;262(108709):108709. doi: 10.1016/j.pharmthera.2024.108709 [DOI] [PubMed] [Google Scholar]

[cit0175] [175].Chiba T, Cerqueira DM, Li Y, et al. Endothelial-derived miR-17 approximately 92 promotes angiogenesis to protect against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2021;32(3):553–562. doi: 10.1681/ASN.2020050717 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0176] [176].Zhao B, Li H, Liu J, et al. MicroRNA-23b targets ras GTPase-activating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy. J Am Soc Nephrol. 2016;27(9):2597–2608. doi: 10.1681/ASN.2015030300 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0177] [177].Wang P, Huang Z, Peng Y, et al. Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair. Nat Commun. 2022;13(1):6502. doi: 10.1038/s41467-022-34287-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0178] [178].Kolling M, Seeger H, Haddad G, et al. The circular RNA ciRs-126 predicts survival in critically ill patients with acute kidney injury. Kidney Int Rep. 2018;3(5):1144–1152. doi: 10.1016/j.ekir.2018.05.012 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0179] [179].Bai S, Xiong X, Tang B, et al. Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-kappaB/MMP-2 axis. Cell Death Dis. 2020;11(11):1008. doi: 10.1038/s41419-020-03169-3 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0180] [180].Satake E, Saulnier PJ, Kobayashi H, et al. Comprehensive search for novel circulating miRNAs and axon guidance pathway proteins associated with risk of ESKD in diabetes. J Am Soc Nephrol. 2021;32(9):2331–2351. doi: 10.1681/ASN.2021010105 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0181] [181].Lorenzen JM, Schauerte C, Kielstein JT, et al. Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury. Clin Chem. 2015;61(1):191–201. doi: 10.1373/clinchem.2014.230359 [DOI] [PubMed] [Google Scholar]

[cit0182] [182].Mao W, Wang K, Xu B, et al. Cirs-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma. Mol Cancer. 2021;20(1):142. doi: 10.1186/s12943-021-01443-2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0183] [183].Wen JH, Li DY, Liang S, et al. Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis. Front Immunol. 2022;13(946832). doi: 10.3389/fimmu.2022.946832 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0184] [184].Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 2020;16(9):489–508. doi: 10.1038/s41581-020-0309-2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0185] [185].Liang S, Wu YS, Li DY, et al. Autophagy and renal fibrosis. Aging Dis. 2022;13(3):712–731. doi: 10.14336/AD.2021.1027 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0186] [186].Guo L, Tan K, Luo Q, et al. Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy. Bosn J Basic Med Sci. 2020;20(3):372–380. doi: 10.17305/bjbms.2019.4410 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0187] [187].Williams RM, Jaimes EA, Heller DA. Nanomedicines for kidney diseases. Kidney Int. 2016;90(4):740–745. doi: 10.1016/j.kint.2016.03.041 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0188] [188].Tsai YC, Teng IL, Jiang ST, et al. Safe nanocomposite-mediated efficient delivery of MicroRNA plasmids for autosomal dominant polycystic kidney disease (ADPKD) therapy. Adv Healthc Mater. 2019;8(5):e1801358. doi: 10.1002/adhm.201801358 [DOI] [PubMed] [Google Scholar]

[cit0189] [189].Al-Tantawy SM, Eraky SM, Eissa LA. Promising renoprotective effect of gold nanoparticles and dapagliflozin in diabetic nephropathy via targeting miR-192 and miR-21. J Biochem Mol Toxicol. 2023;37(10):e23430. doi: 10.1002/jbt.23430 [DOI] [PubMed] [Google Scholar]

[cit0190] [190].Morishita Y, Imai T, Yoshizawa H, et al. Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo. Int J Nanomedicine. 2015;10(3475–88):3475. doi: 10.2147/IJN.S82587 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0191] [191].Zhang Y, Li Y, Lin C, et al. Dioscin-loaded zein nanoparticles alleviate lipopolysaccharide-induced acute kidney injury via the microRNA-let 7i signalling pathways. IET Nanobiotechnol. 2021;15(5):465–472. doi: 10.1049/nbt2.12051 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0192] [192].Gootenberg JS, Abudayyeh OO, Kellner MJ, et al. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science. 2018;360(6387):439–444. doi: 10.1126/science.aaq0179 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0193] [193].Broto M, Kaminski MM, Adrianus C, et al. Nanozyme-catalysed CRISPR assay for preamplification-free detection of non-coding RNAs. Nat Nanotechnol. 2022;17(10):1120–1126. doi: 10.1038/s41565-022-01179-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0194] [194].Li S, Wu H, Chen LL. Screening circular RNAs with functional potential using the RfxCas13d/BSJ-gRNA system. Nat Protoc. 2022;17(9):2085–2107. doi: 10.1038/s41596-022-00715-5 [DOI] [PubMed] [Google Scholar]

[cit0195] [195].Wang W, Zhang M, Ren X, et al. Single-cell dissection of cellular and molecular features underlying mesenchymal stem cell therapy in ischemic acute kidney injury. Mol Ther. 2023;31(10):3067–3083. doi: 10.1016/j.ymthe.2023.07.024 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0196] [196].Fan X, Zhang X, Wu X, et al. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol. 2015;16(1):148. doi: 10.1186/s13059-015-0706-1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0197] [197].Jones D. Setbacks shadow microRNA therapies in the clinic. Nat Biotechnol. 2018;36(10):909–910. doi: 10.1038/nbt1018-909 [DOI] [PubMed] [Google Scholar]

[cit0198] [198].Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–222. doi: 10.1038/nrd.2016.246 [DOI] [PubMed] [Google Scholar]

[cit0199] [199].He AT, Liu J, Li F, et al. Targeting circular RNAs as a therapeutic approach: current strategies and challenges. Signal Transduct Target Ther. 2021;6(1):185. doi: 10.1038/s41392-021-00569-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0200] [200].Xia S, Feng J, Lei L, et al. Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform. 2017;18(6):984–992. doi: 10.1093/bib/bbw081 [DOI] [PubMed] [Google Scholar]

[cit0201] [201].Zhao Q, Liu J, Deng H, et al. Targeting mitochondria-located circRNA SCAR alleviates NASH via reducing mROS output. Cell. 2020;183(1):76–93 e22. doi: 10.1016/j.cell.2020.08.009 [DOI] [PubMed] [Google Scholar]

[cit0202] [202].Yi Z, Zhao Y, Yi Z, et al. Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice. Genome Biol. 2023;24(1):243. doi: 10.1186/s13059-023-03086-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0203] [203].Fan L, Yao L, Li Z, et al. Exosome-based mitochondrial delivery of circRNA mSCAR alleviates sepsis by orchestrating macrophage activation. Adv Sci (Weinh). 2023;10(14):e2205692. doi: 10.1002/advs.202205692 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0204] [204].Wu N, Qadir J, Yang BB. CircRNA perspective: new strategies for RNA therapy. Trends Mol Med. 2022;28(4):343–344. doi: 10.1016/j.molmed.2022.02.002 [DOI] [PubMed] [Google Scholar]

[cit0205] [205].Fromm B, Zhong X, Tarbier M, et al. The limits of human microRNA annotation have been met. RNA. 2022;28(6):781–785. doi: 10.1261/rna.079098.122 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0206] [206].Guo J, Yang Z, Yang X, et al. MiR-346 functions as a pro-survival factor under ER stress by activating mitophagy. Cancer Lett. 2018;413(69):69–81. doi: 10.1016/j.canlet.2017.10.030 [DOI] [PubMed] [Google Scholar]

[cit0207] [207].Wang Y, Liu T, Wu Y, et al. Lipid homeostasis in diabetic kidney disease. Int J Biol Sci. 2024;20(10):3710–3724. doi: 10.7150/ijbs.95216 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0208] [208].Bhatia D, Choi ME. Autophagy and mitophagy: physiological implications in kidney inflammation and diseases. Am J Physiol Renal Physiol. 2023;325(1):F1–F21. doi: 10.1152/ajprenal.00012.2023 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0209] [209].Kaushal GP, Chandrashekar K, Juncos LA. Molecular interactions between reactive oxygen species and autophagy in kidney disease. Int J Mol Sci. 2019;20(15):3791. doi: 10.3390/ijms20153791 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0210] [210].Zhao H, Yang M, Han Y, et al. HIF-1alpha/BNIP3-mediated endoplasmic reticulum degradation via autophagy protects against ischemia reperfusion-induced acute kidney injury. Antioxid Redox Signal. 2025;42(4–6):212–227. doi: 10.1089/ars.2023.0467 [DOI] [PubMed] [Google Scholar]

[cit0211] [211].Morleo M, Brillante S, Formisano U, et al. Regulation of autophagosome biogenesis by OFD1-mediated selective autophagy. Embo J. 2021;40(4):e105120. doi: 10.15252/embj.2020105120 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0212] [212].Sureshbabu A, Ryter SW, Choi ME. Oxidative stress and autophagy: crucial modulators of kidney injury. Redox Biol. 2015;4(208):208–214. doi: 10.1016/j.redox.2015.01.001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0213] [213].Livingston MJ, Ding HF, Huang S, et al. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy. 2016;12(6):976–998. doi: 10.1080/15548627.2016.1166317 [DOI] [PMC free article] [PubMed] [Google Scholar]

[cit0214] [214].Li Z, Hao S, Yin H, et al. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice. Behav Brain Res. 2016;305(265):265–277. doi: 10.1016/j.bbr.2016.03.023 [DOI] [PubMed] [Google Scholar]

PERMALINK

Non-coding RNAs regulate autophagy in kidney disease: friend or foe?

Yankun Li

Tongtong Ma

Xinhua Liang

Tingting Jin

Xingqi Zhao

Junmin Huang

Junfeng Hao

Huafeng Liu

Peng Wang

Roles

ABSTRACT

Introduction

The definition and diverse mechanisms of ncRNAs

Figure 1.

miRNAs

lncRNAs

circRNAs

Autophagy

Classification

Process

Signaling pathways on autophagy regulation

Figure 2.

Autophagy in kidney disease

Autophagy in RCC

Autophagy in AKI

Autophagy in chronic kidney disease

Regulation of autophagy in RCC by ncRNAs

Regulation of autophagy in RCC by miRNAs

Inhibition of autophagy in RCC by miRNAs

Promotion of autophagy in RCC by miRNAs

Regulation of autophagy in RCC by lncRNAs

Inhibition of autophagy in RCC by lncRNAs

Promotion of autophagy in RCC by lncRNAs

Regulation of autophagy in RCC by ceRNA-miRNA axes

Inhibition of autophagy in RCC by ceRNA-lncRNA axes

Promotion of autophagy in RCC by ceRNA-miRNA axes

Figure 3.

Table 1.

Regulation of autophagy in AKI by ncRNAs

Regulation of autophagy in AKI by miRNAs

Inhibition of autophagy in AKI by miRNAs

Promotion of autophagy in AKI by miRNAs

Regulation of autophagy in AKI by lncRNAs

Regulation of autophagy in AKI by circRNAs

Regulation of autophagy in AKI by the ceRNA-miRNA axes

Inhibition of autophagy in AKI by the ceRNA-miRNA axes

Promotion of autophagy in AKI by the ceRNA-miRNA axes

Figure 4.

Table 2.

Regulation of autophagy in CKD by ncRNAs

Regulation of autophagy in CKD by miRNAs

Inhibition of autophagy in CKD by miRNAs

Promotion of autophagy in CKD by miRNAs

Regulation of autophagy in CKD by lncRNAs

Inhibition of autophagy in CKD by lncRNAs

Promotion of autophagy in CKD by lncRNAs

Regulation of autophagy in CKD by ceRNA-miRNA axes

Inhibition of autophagy in CKD by ceRNA-miRNA axes

Promotion of autophagy in CKD by ceRNA-miRNA axes

Figure 5.

Table 3.

ncRNAs regulate autophagy in other kidney diseases

Kidney stone

IgA nephropathy

Lupus nephritis

Focal and segmental glomerulosclerosis (FSGS)

Table 4.

Clinical applications of non-coding RNAs by autophagy regulation in kidney diseases

Table 5.

ncRNAs as autophagy-related diagnostic biomarkers

Therapeutic targeting of autophagy via ncRNAs

Emerging technologies in ncRNAs-based diagnostics and therapeutics

Current challenges

Conclusions and future perspectives

Funding Statement

Disclosure statement

References

ACTIONS