Skip to main content
NCBI home page
Heliyon logoLink to Heliyon
. 2024 Mar 9;10(6):e27631. doi: 10.1016/j.heliyon.2024.e27631

lncRNA SNHG1 promotes the progression of hepatocellular carcinoma by regulating the miR-7-5p/IGF2BP2 axis

Xianggao Zhu a,b,c,1, Hongfang Yu a,b,1, Hong Li a,b,1, Wei Zhang a,b, Liping Sun a,b, Ting Dou a,b, Zhenfei Wang d, Haiping Zhao e,⁎⁎, Hao Yang a,b,⁎
PMCID: PMC10966585  PMID: 38545199

Abstract

Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) plays a crucial role in the occurrence and progression of various tumors. This study investigates the function of lncRNA SNHG1 in hepatocellular carcinoma (HCC). We discovered that lncRNA SNHG1 is significantly upregulated in HCC and markedly enhances cell proliferation, migration, and invasion, while simultaneously suppressing apoptosis in HCC cells. Furthermore, lncRNA SNHG1 was found to downregulate miR-7-5p expression. Overexpression of lncRNA SNHG1 counteracted the suppression of HCC cell migration, proliferation, and invasion caused by miR-7-5p mimics, and reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. Additionally, miR-7-5p was shown to negatively regulate IGF2BP2, with the silencing of IGF2BP2 diminishing the abilities of HCC cells to proliferate, migrate, and invade, and increasing their propensity for apoptosis. Overexpression of lncRNA SNHG1 negated these effects. Thus, lncRNA SNHG1 fosters HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p.

Keywords: lncRNA SNHG1, Hepatocellular carcinoma, IGF2BP2, Progression, miR-7-5p

1. Introduction

Liver cancer, one of the deadliest malignancies within the human digestive system, poses a significant threat to public health [1]. In the United States alone, it is estimated that there will be 42,810 new cases of liver cancer, resulting in 30,160 [2] fatalities. The disease encompasses two primary categories: primary liver cancer and metastatic liver cancer [3]. Primary liver cancer represents 5.6% of all cancer cases, with hepatocellular carcinoma (HCC) being the predominant type, accounting for 80–90% of primary liver cancer [4] cases. HCC is characterized by its aggressive nature, with insidious onset, rapid progression, and poor prognosis [5,6]. Treatment options for patients with HCC include liver transplantation, surgical resection, percutaneous ablation, radiation therapy, transarterial and systemic adjuvant therapies [[7], [8], [9]]. Additionally, emerging treatments, such as trans-arterial chemoembolization combined with systemic medications [10] and Atezolizumab-bevacizumab regimen alongside 90Yttrium transarterial radioembolization [11], are under development. Despite these efforts, the prognosis for HCC patients has not significantly improved due to the cancer's tendency to metastasize [12,13]. A deeper understanding of HCC mechanisms is crucial for identifying novel targets and enhancing treatment strategies, thereby surpassing the current treatment limitations.

Long noncoding RNAs (LncRNAs) have emerged as promising therapeutic targets for HCC. LncRNAs play roles in the occurrence and progression of multiple tumors, acting as either oncogenes or tumor suppressors in conditions such as acute myeloid leukemia [14], breast cancer [15], HCC [16], and melanomas [17]. These molecules can regulate gene expression through multiple mechanisms, including modulating transcription factor binding to target genes, serving as decoys for miRNAs to protect targeted mRNAs [18] from degradation, and functioning as scaffolds to regulate protein-protein interactions and their subsequent signaling pathways. Consequently, numerous studies have highlighted the significant impact of the long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) on the progression, metastasis, and growth of several cancers, including breast [19], colorectal [20], and pancreatic [21]cancers.

Recent research has shown that lncRNA SNHG1 plays a pivotal role in advancing liver cancer by modulating p53 activity through its interaction with DNMT1 [22]. In cervical cancer, lncRNA SNHG1 has been found to influence NEK2 via specific binding to miR-195, thus enhancing cancer cell migration and invasion [23]. Furthermore, lncRNA SNHG1 supports the proliferation and viability of pancreatic cancer cells while reducing apoptosis by targeting miR-497 to adjust FGFR1 expression [21] levels. These findings underscore the potential of lncRNA SNHG1 as a diagnostic and therapeutic biomarker for cancer. Although preliminary studies suggest that lncRNA SNHG1 may impact HCC progression [24,25], its exact mechanism in HCC is yet to be fully understood. Therefore, this study delves into the role and underlying mechanism of lncRNA SNHG1 in HCC cells and a mouse model, aiming to contribute to the development of innovative therapeutic strategies for HCC.

2. Material and method

2.1. Patients and specimens

The HCC tissues and normal tissues were collected from patients admitted to Inner Mongolia Cancer Hospital (Inner Mongolia, China) from August 2021 to August 2022. The clinical characteristics of the HCC patients are detailed in Table 1. The study protocols received approval from the hospital's ethics committee (YKD202201172), adhered to the Helsinki guidelines, and were conducted with informed consent from all participants. The study's workflow is illustrated in Fig. 1.

Table 1.

The clinical information of patients.

No. TNM Stage Age Gender Maximum tumor diameter (cm)
1 IIIA 69 Male 16*11
2 IV 58 Male 6*5
3 II 46 Male 7.5*6
4 III 81 Female 5*4.5
5 II 64 Male 11*10
6 III 55 Male 12*10
7 II 58 Male 3*2.5
8 III1 46 Male 11.2*9
9 III 52 Male 7.2*8
10 III 77 Male 9.5*8.7
11 ⅢB 70 Female 18
12 ⅠB 83 Female 6.5
Open in a new tab

Fig. 1.

Fig. 1

Open in a new tab

The flowchart of this study.

2.2. Cell culture and transfection

Five HCC cell lines (HepG2, SNU398, bel-7404, Huh7, Li-7) and a normal hepatic cell line (LO2) were procured from Beinan bio (Beijing, China). All cell lines were maintained in DMEM medium (C11995500BT, Thermo Fisher, New York, USA) supplemented with 10% fetal bovine serum (TB-534237681231, Thermo Fisher, New York, USA) in a humidified atmosphere at 37 °C and 5% CO2. pcDNA3.1/SNHG1, pcDNA3.1 NC, si-SNHG1, si-NC, pcDNA3.1/IGF2BP2, si-IGF2BP2 and si-NC were sourced from RiboBio (Guangzhou, China). HepG2 cells were transfected with pcDNA3.1/SNHG1, si-SNHG1, pcDNA3.1/IGF2BP2, si-IGF2BP2 and co-transfected with si-SNHG1+pcDNA3.1/IGF2BP2, pcDNA3.1/SNHG1+si-IGF2BP2, respectively, through Lipofectamine 2000 (12,566,014, Thermo Fisher, New York, USA), following the manufacturer's instructions.

2.3. Mouse model

Fifteen six-week-old female nude BALB/c mice were procured from Institute of Zoology, Chinese Academy of Sciences (Beijing, China) and housed under a 12-h light-dark cycle, with ad libitum access to food and water. Following a one-week acclimatization period, mice were divided into five groups: pcDNA3.1/SNHG1, pcDNA3.1/NC, si-NC, si-SNHG1, and a control group. HepG2 cells treated with pcDNA3.1/SNHG1, pcDNA3.1/NC, si-NC, and si-SNHG1 were subcutaneously injected into the mice. Once the tumors reached a volume of 50 mm3, the mice were administered SNHG1-OE or SNHG1-shRNA plasmids three times weekly for four weeks. Tumor volume and weight were monitored and recorded every seven days over a 28-day period. All procedures involving animals were conducted in strict accordance with the ethical standards of the Inner Mongolia Cancer Hospital (Inner Mongolia, China), adhering to institutional guidelines.

2.4. qRT-PCR analysis

Total RNA was extracted using Redzol (FTR-50, SaiBaiSheng Biotech Co., Ltd, Beijing, China). cDNA synthesis was performed using PrimeScript™ RT reagent kit (QP057, iGeneBio, Guangzhou, China). The RT-PCR was implemented using 2 × SYBR Green qPCR Master Mix (Servicebio, Wuhan, China) on iQ5 Real-Time PCR amplicon (Applied Biosystems, ThermoFisher, New York, USA). The amplification protocol included an initial denaturation step at 95 °C for 30 s, followed by 40 cycles of denaturation at 95 °C for 15 s and extension at 60 °C for 30 s. GAPDH was used as reference gene, with primers listed in Table 2 mRNA expression levels were quantified using 2-ΔΔCt.

Table 2.

The primer sequences used in this study.

Gene Primer sequence
GAPDH Forward: 5′-TCAGCAATGCCTCCTGCAC-3′
Reverse: 5′-TCTGGGTGGCAGTGATGGC-3′
IGF2BP2 Forward: 5′-TGGGACAGTGGAGAATGTGG-3′
Reverse: 5′-GCATGCTTCAGAAGTCCCCT-3′
SNHG1 Forward: 5′-TAACCTGCTTGGCTCAAAGGG-3′
Reverse: 5′-CAGCCTGGAGTGAACACAGA-3′
hsa-miR-7-5p Forward: 5′- GCGCTGGAAGACTAGTGATTTTGTTGTT-3′
Reverse: 5′-TGGTGTCGTGGAGTCG-3′
U6 Forward:5′-CTTCGGCAGCACATATAC-3′
Reverse: 5′-GAACGCTTCACGAATTTGC-3′
si-NC 5′-UUCUCCGAACGUGUCACGUTT-3′
si-IGF2BP2 Forward: 5′-UCGAAUCUGAAUUUUCCUGCU-3′
Reverse: 5′-CAGGAAAAUUCAGAUUCGAAA-3′
ASO-miR-7-5p Forward: 5′-AACAAAAUCACUAGUCUUCCA-3′
Reverse: 5′-GAAGACUAGUGAUUUUGUUGU-3′
si-SNHG1 Forward: 5′-AAGAACUUGGAAAAUUCACCU-3′
Reverse: 5′-GUGAAUUUUCCAAGUUCUUGG-3′
Open in a new tab

2.5. Western blotting (WB) analysis

Proteins were extracted using RIPA buffer (R002, Solarbio Science & Technology Co., Ltd, Beijing, China). The lysates underwent centrifugation at 14,000×g for 20 min at 4 °C, and supernatant containing total protein was collected. Proteins were separated by SDS-PAGE and transferred onto PVDF membranes (Cat.NO.IPVH00010, Millipore, Boston, USA) using Tris-glycine transfer buffer (AR0138, Boster Biological Technology Co., Ltd, Wuhan, China) for 2 h at 4 °C. Membranes were blocked with 5% nonfat dry milk for 2 h and incubated overnight at 4 °C with primary antibodies at a dilution of 1:1000). Subsequently, the membranes were washed with 1 × TBST and incubated with secondary antibody for 1.5 h. The primary antibodies used included Anti-Caspase3 (ab184787, Abcam), Anti-Caspase9 (ab202068, Abcam), Anti-Bax (ab32503, Abcam), Anti-Bcl (ab182858, Abcam), and Anti-GAPDH (ab9485, Abcam). HRP-labeled Goat anti-rabbit IgG (ab6721) served as the secondary antibody. After four washes with 1 × TBST, membranes were developed using Western Lightning™ Chemiluminescence Reagent for 30 s. Protein bands were visualized using an Epson Perfection V39 scanner (Seiko Epson, Tokyo, Japan). Anti-GAPDH antibody (ab8226, Abcam) was used as the loading control.

2.6. Cell proliferation assay

Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay kit (AR1191, Boster Biological Technology., LTD, Wuhan, China) and colony formation assays. For the CCK-8 assay, cells (1000 cells/well) were plated in 96-well plates and treated with CCK-8 solution at 0 h, 24 h, 48 h, and 72 h. The absorbance was measured at 450 nm using an enzyme-linked immunosorbent assay reader (DNM9606, Beijing Perlong Technology Co., Ltd, Beijing, China).

In the colony formation assay, cells were treated with 0.25% trypsin-EDTA (T1300, Solarbio Co., Ltd. Beijing, China). The reaction was stopped by adding complete medium containing 10% FBS (tb-534237681231, GIBCO, New York, USA). After 1–2 weeks of incubation, cells were fixed with 4% paraformaldehyde for 30 min at 4 °C and stained with 0.5 mL of 0.1% crystal violet (C8470, Solarbio Co., Ltd. Beijing, China). Subsequently, cells were rinsed with PBS, and colonies were photographed.

2.7. Dual-luciferase reporter assay

The dual-luciferase reporter vectors containing either the wild-type SNHG1 3′UTR (SNHG1 wt) or its mutant form (SNHG1 mut), as well as the wild-type IGF2BP2 3′UTR (IGF2BP2 wt) or its mutant form (IGF2BP2 mut), were constructed using the pmirGLO dual-luciferase vector (Cosmo bio, Tianjin, China). Cells were co-transfected with these vectors along with miR-7-5p mimics or ASO-miR-7-5p. Dual Luciferase Reporter Gene Assay Kit (11405ES60, Yeasen Biotechnology Co., Ltd. Shanghai, China) was applied to detect the luciferase activity.

2.8. Cell migration assay

Cells cultured to near confluence were linearly scratched using a pipette tip and subsequently incubated in serum-free medium at 37 °C with 5% CO2. Images were captured at 0 and 24 h using a SOPTOP OD630K inverted microscope (Shunyu Hengping Scientific Instrument Co., Ltd. Shanghai, China).

2.9. Transwell assay

Cells were rinsed with PBS, treated with 0.25% trypsin-EDTA (T1300, Solarbio Co., Ltd. Beijing, China), and resuspended in complete medium containing 0.5 mL 10% FBS (tb-534237681231, GIBCO, New York, USA) to terminate digestion. Transwell assay was performed as previously described [26]. Images were obtained using inverted microscope (SOPTOP OD630K, Shunyu Hengping Scientific Instrument Co., Ltd., Shanghai, China).

2.10. Apoptosis assay

Cell concentration was adjusted to 5 × 104-105/L, followed by centrifugation to collect the supernatant. Apoptosis was detected utilizing Annexin V-FITC/PI apoptosis kit (AP101-100-kit, Multisciences (lianke) biotechco., ltd, Zhejiang, China) on a BD FACSCaliburTM Flow Cytometer (E97501093, San Jose, CA, USA). Apoptosis rate = early apoptotic rate + late apoptotic rate.

In mice, the apoptosis was measured using the TUNEL FITC apoptosis detection Kit (Boster Biological Technology., LTD, Wuhan, China), following the previously [27] described protocol. Fluorescence microscopy images were captured using a fluorescence microscope (BH2-RFCA, OLYMPUS, Japan).

2.11. Hematoxylin-eosin (HE) staining

Mouse tissues were fixed, embedded in paraffin, and sectioned. The sections were dried at 45 °C, then deparaffinized in xylene twice for 10 min each time. Following this, they were sequentially dehydrated in a graded ethanol series (100%, 95%, 85%, 70%, and 50%) for 0.5–1 min at each concentration and washed in PBS twice for 5 min each. The sections were stained with hematoxylin for 2 min, differentiated in HCl-alcohol solution three times for 2 s each, and rinsed in distilled water. They were then counterstained with 1% eosin for 10–15 s and dehydrated again through the graded ethanol series (50%, 70%, 85%, 95%, and 100%) for 0.5–1 min at each step. Finally, the sections were cleared, mounted with neutral gum, and examined under an inverted microscope (SOPTOP OD630K, Shunyu Hengping Scientific Instrument Co., Ltd., Shanghai, China).

2.12. Immunocytochemistry

Mouse tissue sections were blocked and then incubated overnight with Anti-ki67 Rabbit antibody (1: 100, SANGON, Shanghai, China) at 4 °C. Subsequently, they were incubated with Cy3-conjugated Goat anti-Rabbit IgG (1:100, SANGON, Shanghai, China) at 37 °C for 60 min. Following this, the sections were counterstained with DAPI and visualized under an inverted fluorescence Microscope (BH2-RFCA, OLYMPUS, Japan) at 550 nm.

3. Results

3.1. The high lncRNA SNHG1 expression promoted the progression of HCC in vitro

Initially, we evaluated lncRNA SNHG1 expression levels in HCC, finding significantly higher expression in HCC samples (374 samples) compared to normal tissues (50 samples), as illustrated in Fig. 2A. Further analysis confirmed elevated levels of lncRNA SNHG1 in both HCC tissues and cell lines (Fig. 2B and C). Subsequently, we engineered HepG2 cells to overexpress (pcDNA3.1/SNHG1) or silence (si-SNHG1) lncRNA SNHG1. Results showed an upregulation of lncRNA SNHG1 in pcDNA3.1/SNHG1 group relative to pcDNA3.1-NC group, and a downregulation in si-SNHG1 group compared to si-NC group (Fig. 2D). Notably, overexpression of lncRNA SNHG1 significantly enhanced proliferation (Fig. 2E 2F), migration (Fig. 2G), and invasion (Fig. 2H) capabilities of HepG2 cells while substantially reducing apoptosis (Fig. 2I). Conversely, silencing lncRNA SNHG1 markedly decreased cell proliferation (Fig. 2E and F), migration (Fig. 2G), and invasion (Fig. 2H), and significantly increased apoptosis (Fig. 2I) of HepG2 cells. In addition, compared to pcDNA3.1 NC group, the pro-apoptotic protein (caspase-3, caspase-9, Bax) levels were reduced and anti-apoptotic protein (Bcl-1) levels was improved in pcDNA3.1/SNHG1 group (Fig. 2J). In contrast, compared to si-NC group, the caspase-3, caspase-9 and Bax levels were improved and Bcl-1 level was reduced in si-SNHG1 group (Fig. 2J,Fig. S1). These findings collectively indicate that high expression of lncRNA SNHG1 significantly contributes to the progression of HCC in vitro.

Fig. 2.

Fig. 2

Open in a new tab

The high lncRNA SNHG1 expression promoted the progress of HCC in vitro. A-B-C. The expression of lncRNA SNHG1 in HCC tissues and cells. D. pcDNA3.1/SNHG1 and si-SNHG1 transfection efficiency in HepG2 cells were assessed via qRT-PCR. E. CCK-8 assay was performed at 0 h, 24 h, 48 h and 72 h to determine the proliferation of HepG2 cells treated with pcDNA3.1/SNHG1 and si-SNHG1. F. The colony formation abilities of HepG2 cells treated with pcDNA3.1/SNHG1 and si-SNHG1. G. The migration of HepG2 cells treated with pcDNA3.1/SNHG1 and si-SNHG1. H. The invasion of HepG2 cells treated with pcDNA3.1/SNHG1 and si-SNHG1. I. The apoptosis rate of HepG2 cells treated with pcDNA3.1/SNHG1 and si-SNHG1. J. The pro-apoptotic proteins (caspase-3, caspase-9, Bax) and anti-apoptotic protein (Bcl-1) were performed through Western blot. *p < 0.05, **p < 0.01, p*** <0.001.

3.2. lncRNA SNHG1 targeted miR-7-5p in HCC cells

Previous researches have revealed that the miR-7-5p upregulation could reduce the proliferation, migration and accelerate apoptosis in HCC cells [28]. Building on this foundation, we explored the possibility that lncRNA SNHG1 could drive tumor progression by modulating miR-7-5p. To this end, we identified potential binding sites between lncRNA SNHG1 and miR-7-5p (Fig. 3A). The luciferase activity was remarkably reduced in miR-7-5p mimics group than mimics-NC group in pmirSNHG1 wt cells (Fig. 3B). The luciferase activity was observably enhanced in ASO-miR-7-5p group than ASO-NC group, but remained unchanged in cells harboring the pmirSNHG1 mutant vector (Fig. 3B). In addition, the miR-7-5p expression was remarkably reduced in pcDNA3.1/SNHG1 group and notably increased in si-SNHG1 group (Fig. 3C). These findings confirm that lncRNA SNHG1 exerts a negative regulatory effect on miR-7-5p expression in vitro.

Fig. 3.

Fig. 3

Open in a new tab

lncRNA SNHG1 targeted miR-7-5p in HCC cells. A. The binding site of lncRNA SNHG1 and miR-7-5p. B. The luciferase activity was detected by luciferase assay in the cells co-transfected with wild-type SNHG1 3′UTR (SNHG1 wt) or mutant SNHG1 3′UTR (SNHG1 mut) plasmids and miR-7-5p or ASO- miR-7-5p. C. The expression of miR-7-5P in pcDNA3.1/SNHG1 and si-SNHG1 groups. *p < 0.05, **p < 0.01, p*** <0.001.

3.3. lncRNA SNHG1 facilitated the progression of HCC by targeting to regulate the miR-7-5p expression

We explored the mechanism by which lncRNA SNHG1 might influence HCC progression through targeting miR-7-5p. The introduction of miR-7-5p mimics was observed to reduce the proliferative capacity of cells over a period of 0–72 h, whereas co-transfection with pcDNA3.1/SNHG1 and miR-7-5p mimics counteracted this suppressive effect (Fig. 4A). The overexpression of lncRNA SNHG1 restored the repression of cell migration induced by miR-7-5p mimics (Fig. 4B). Regarding cell invasion, lncRNA SNHG1 overexpression likewise negated the inhibitory impact of miR-7-5p mimics on this cellular function (Fig. 4C). In addition, the combination of pcDNA3.1/SNHG1 and miR-7-5p mimics significantly mitigated the enhanced apoptotic effect induced by miR-7-5p mimics alone (Fig. 4D). Collectively, these findings underscore that lncRNA SNHG1 advances HCC progression by specifically targeting to miR-7-5p in vitro.

Fig. 4.

Fig. 4

Open in a new tab

lncRNA SNHG1 promoted the progression of HCC by targeting to regulate the miR-7-5p expression. A. CCK-8 assay was performed at 0 h, 24 h, 48 h and 72 h to determine the proliferation of cells co-transfected with pcDNA3.1/SNHG1 or si-SNHG1 and miR-7-5p mimics or ASO-miR-7-5p. B. The migration of cells co-transfected with pcDNA3.1/SNHG1 or si-SNHG1 and miR-7-5p mimics or ASO-miR-7-5p. C. The invasive of cells co-transfected with pcDNA3.1/SNHG1 or si-SNHG1 and miR-7-5p mimics or ASO-miR-7-5p. D. The apoptosis rete of cells co-transfected with pcDNA3.1/SNHG1 or si-SNHG1 and miR-7-5p mimics or ASO-miR-7-5p. *p < 0.05, **p < 0.01, p*** <0.001.

3.4. miR-7-5p targeted IGF2BP2 to negatively regulate its expression

Emerging evidences indicated that IGF2BP2, an N6-methyladenosine (m6A) reader, plays a crucial role in cancer progression by interacting with lncRNAs, miRNAs, and m6A-related genes [29]. In light of this, we pinpointed the binding sites between IGF2BP2 and miR-7-5p through targeted gene prediction analysis (Fig. 5A). The luciferase assay results revealed a significant decrease in luciferase activity in miR-7-5p mimics group compared to mimics-NC group in pmirIGF2BP2 wt cells (Fig. 5B). The luciferase activity was significantly lowered in ASO-miR-7-5p group relative to the ASO-NC group, an effect not observed in cells with the mutant pmirIGF2BP2 vector (Fig. 5B). Furthermore, we assessed IGF2BP2 mRNA levels across different groups—mimics-NC, miR-7-5p mimics, ASO-NC, and ASO-miR-7-5p—discovering that IGF2BP2 mRNA levels were decreased in miR-7-5p mimics group and increased in ASO-miR-7-5p group (Fig. 5C). These findings indicated that miR-7-5p targets IGF2BP2, leading to a negative regulation of its expression.

Fig. 5.

Fig. 5

Open in a new tab

miR-7-5p targeted IGF2BP2 to negatively regulate its expression. A. The binding site of IGF2BP2 and miR-7-5p. B. The luciferase activity was detected by luciferase assay in the cells co-transfected with wild-type SNHG1 3′UTR (SNHG1 wt) or mutant SNHG1 3′UTR (SNHG1 mut) plasmids and miR-7-5p mimics or ASO-miR-7-5p. C. The level of IGF2BP2 mRNA in mimics-NC, miR-7-5p mimcs, ASO-NC and ASO-miR-7-5p groups. p*** <0.001.

3.5. lncRNA SNHG1 promoted the progression of HCC by promoting IGF2BP2 expression by targeting the miR-7-5p in vitro

To elucidate the impact of lncRNA SNHG1 on miR-7-5p-mediated regulation of IGF2BP2, we engineered HepG2 cells to overexpress IGF2BP2 (pcDNA3.1/IGF2BP2), simultaneously silence lncRNA SNHG1 and overexpress IGF2BP2 (si-SNHG1+pcDNA3.1/IGF2BP2), silence IGF2BP2 (si-IGF2BP2), and both overexpress lncRNA SNHG1 and silence IGF2BP2 (pcDNA3.1/SNHG1+si-IGF2BP2). The pcDNA3.1/IGF2BP2 group exhibited enhanced proliferation (Fig. 6A), migration (Fig. 6B), and invasion (Fig. 6C) capabilities, along with a reduction in apoptosis capacity (Fig. 6D), compared to pcDNA3.1NC group. Conversely, silencing IGF2BP2 led to a decrease in proliferation (Fig. 6A), migration (Fig. 6B), and invasion (Fig. 6C) abilities, and an increase in apoptosis (Fig. 6D) of HepG2 cells. Notably, overexpression of lncRNA SNHG1 reversed the effects induced by IGF2BP2 silencing. Taken together, the results suggested that lncRNA SNHG1 accelerates HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p in vitro.

Fig. 6.

Fig. 6

Open in a new tab

lncRNA SNHG1 promoted the progression of HCC by promoting the expression of IGF2BP2 by targeting the miR-7-5p. The proliferation (A), migration (B), invasion (C) abilities and apoptosis capacity (D) of cells co-transfected with pcDNA3.1SNHG1 or si-SNHG1 and si-IGF2BP2 or pcDNA3.1IGF2BP2. *p < 0.05, **p < 0.01, p*** <0.001.

3.6. lncRNA SNHG1 accelerated the progression of HCC by targeting to regulate the miR-7-5p expression to promote IGF2BP2 expression in vivo

To explore the role of lncRNA SNHG1 in the progression of HCC in vivo, we established mouse models with either overexpression of lncRNA SNHG1 (pcDNA3.1/SNHG1) or silencing of lncRNA SNHG1 (si-SNHG1). The tumor volume and weight of mice were significantly increased in the lncRNA SNHG1 group compared to si-SNHG1 group (Fig. 7A). Histological examination revealed that cancer cells in pcDNA3.1/SNHG1 group were denser and more robust, whereas cells in si-SNHG1 group showed signs of shrinkage and necrosis (Fig. 7B). Further analysis of miR-7-5p and IGF2BP2 expression showed a significant decrease in miR-7-5p levels and a corresponding increase in IGF2BP2 expression in pcDNA3.1/SNHG1 group (Fig. 7C). In addition, the apoptotic rate was lower in the pcDNA3.1/SNHG1 group compared to si-SNHG1 group (Fig. 7D), with a decrease in pro-apoptotic markers (caspase-3, caspase-9, and Bax) and an increase in the anti-apoptotic marker Bcl-2 (Fig. 7E,Fig. S2). IGF2BP2 protein levels were also elevated in the pcDNA3.1/SNHG1 group relative to the si-SNHG1 group (Fig. 7E,Fig. S2). Moreover, cell proliferation in HCC was significantly higher in lncRNA SNHG1 group than in si-SNHG1 group (Fig. 7F). These findings collectively demonstrate that lncRNA SNHG1 enhances the progression of HCC by modulating miR-7-5p expression, thereby upregulating IGF2BP2 expression in vivo.

Fig. 7.

Fig. 7

Open in a new tab

lncRNA SNHG1 promoted the progression of HCC by targeting to regulate the miR-7-5p expression to promote GF2BP2 expression in HCC mice model. A. The tumor weight and volume of mice in pcDNA3.1/SNHG1 and si-SNHG1 group. B. HCC mouse tissues HE staining observation chart. C. The expression of lncRNA SNHG1, miR-7-5p and IGF2BP2 in pcDNA3.1/SNHG1 and si-SHNG1 group. D. The apoptotic rate of HCC mouse cells in pcDNA3.1/SNHG1 group and si-SNHG1 group. E. The expression of IGF2BP2 and level of caspase-3, caspase-9, Bax and Bcl-2 in pcDNA3.1/SNHG1 and si-SNHG1 groups. F. The proliferation of HCC mouse cells in lncRNA SNHG1 and si-SNHG1 groups. *p < 0.05, **p < 0.01, p*** <0.001.

4. Discussion

HCC stands as one of the most common and aggressive forms of liver cancer. Despite of advancements in chemotherapy and surgical interventions, the survival rates for HCC patients remain disappointingly low, largely due to challenges like metastasis and treatment resistance [30,31]. lncRNAs have been identified as key regulators in various biological processes, influencing transcriptional, epigenetic, and post-transcriptional mechanisms, or directly modulating [32] protein activities. Additionally, lncRNAs have emerged as potential biomarkers for diagnosing and treating a wide range of cancers [33,34]. Our study highlights the lncRNA SNHG1/miR-7-5p/IGF2BP2 axis as a critical pathway in HCC progression. The cellular experiments suggested that lncRNA SNHG1 is upregulated in HCC tissues and cells, with its overexpression significantly enhancing cell proliferation, migration, invasion, and notably reducing apoptosis in HepG2 cells. The lncRNA SNHG1 was found to target miR-7-5p, which in turn targets IGF2BP2, leading to its downregulation in HepG2 cells. Our findings indicate that lncRNA SNHG1 propels HCC progression by modulating miR-7-5p to upregulate IGF2BP2 expression in both HCC cells and mice.

Previous studies have documented the role of lncRNA SNHG1 in various cancers, including liver cancer [35]. For instance, Li et al. reported elevated lncRNA SNHG1 levels in liver cancer patients, showing that its overexpression could enhance the proliferative capabilities of liver cancer cells by diminishing p53 expression via DNMT1 binding [22]. LncRNA SNHG1 has also been shown to sequester miR-326, mitigating its inhibitory impact on PKM2, thereby activating the glycolysis pathway in HCC [36]. Furthermore, Li et al. found that lncRNA SNHG1 was overexpressed in sorafenib-resistant HCC cells, contributing to sorafenib-resistance by modulating the Akt pathway through the upregulation of SLC3A2, with its expression being regulated by miR-21 [24]. These insights align with our results, underscoring lncRNA SNHG1's stimulatory role in HCC via facilitating cell proliferation, migration, invasion, and inhibiting apoptosis. Notably, our study reveals that lncRNA SNHG1 exerts a negative regulatory effect on miR-7-5p expression.

Similar to lncRNA SNHG1, miR-7-5p plays a significant role in tumor progression. Wang et al. demonstrated that miR-7-5p was down-regulated in HCC tissues, and its overexpression led to reduced proliferation and migration, and enhanced apoptosis in HCC cells by targeting SPC24 [28]. Additionally, in non-small cell lung cancer (NSCLC), miR-7-5p was also found to be downregulated. Elevated levels of miR-7-5p have been shown to inhibit the progression and metastasis of NSCLC cells by targeting NOVA2 [37]. These studies suggest that miR-7-5p plays a critical role in attenuating cancer progression by modulating the expression of target genes. In the present study, miR-7-5p expression was decreased in pcDNA3.1/SNHG1 group and significantly increased in si-SNHG1 group. lncRNA SNHG1 was able to counteract the suppressive effects of miR-7-5p mimics on HCC cell migration, proliferation, and invasion, and also reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. These findings revealed that lncRNA SNHG1 might enhance the progression of HCC via targeting to regulate the miR-7-5p expression. Moreover, we discovered that miR-7-5p directly targets IGF2BP2, negatively affecting its expression.

IGF2BP2 is a member of the IGF2 mRNA-binding protein family and is recognized as an m6A reader [38]. It has been implicated in the initiation and progression of cancer through interactions with miRNAs, lncRNAs, and mRNAs [[39], [40], [41]]. Pu et al. reported that IGF2BP2 expression was elevated in HCC and that its overexpression was correlated with poorer patient prognosis. IGF2BP2 was shown to promote cancer cell proliferation by directly binding to the m6A site on FEN1 mRNA, thereby regulating FEN1 mRNA levels [42]. We discovered that overexpression of IGF2BP2 enhances proliferation, migration, and invasion capabilities, and decreases apoptosis in HCC cells. Conversely, IGF2BP2 silencing impairs HCC cell progression, an effect that is negated by overexpression of lncRNA SNHG1. These results suggest that lncRNA SNHG1 could drive HCC progression by upregulating IGF2BP2 expression through the targeting of miR-7-5p.

Although our study elucidates the role of lncRNA SNHG1 in the progression of HCC, there are several limitations that warrant attention. Firstly, the precise mechanisms through which lncRNA SNHG1 influences the biological processes underlying HCC development remain to be fully understood. Secondly, the impact of lncRNA SNHG1 on immune cell infiltration and its prognostic significance in HCC are areas that require further exploration in subsequent research. Moreover, the role of lncRNA SNHG1 in the development of HCC should be rigorously validated in the context of clinical trials to confirm its potential as a target for therapeutic intervention.

5. Conclusion

To conclude, our research demonstrates that lncRNA SNHG1/miR-7-5p/IGF2BP2 axis plays a significant role in facilitating the progression of HCC. We hope our findings will contribute to the development of novel diagnostic and therapeutic schedules for HCC.

Ethical approval and consent to participate

All experiments were approved by the ethics committee of Inner Mongolia Cancer Hospital (Inner Mongolia, China) (YKD202201172), conformed to the Helsinki guidelines, and informed consent of all subjects was obtained.

Consent for publication

Not applicable.

Data availability statement

The data supporting the conclusions of this study were included in this article and supplementary materials. The data used and analyzed in the current study are available from the corresponding author upon a reasonable request.

Funding

This study was supported by National Natural Science Foundation of China (81860534, 82260481, 82074144), Natural Science Foundation of Inner Mongolia (2021MS08152, 2021JQ09), Inner Mongolia Autonomous Region Science and Technology Planning Project (201802152, 2019GG039, 2019GG086, 2021GG0167), Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Transformation Application of Organoid in Medical and Industrial Interdiscipline (YKD2022TD002), Major Project of Inner Mongolia Medical University (YKD2022ZD002), Radiotherapy Discipline Construction Project of National Cancer Regional Medical Center for Inner Mongolia Medical University (YKD2022XK009), Radiobiology System and Team Construction of Radiotherapy for Inner Mongolia Medical University (YKD2022XK014), and the Zhi Yuan Talent Projects of Inner Mongolia Medical University (ZY0202011, ZY0130014), the joint project of Inner Mongolia Medical University (YKD2024LH002), Public hospital reform and high-quality development demonstration project research fund, gastrointestinal tumors (2023SGGZ114, 2023SGGZ076), and the Clinical Need Oriented Basic Research Project of Inner Mongolia Academy of Medical Sciences ( 2023GLLHO136, 2023GLLH0142, 2023GLLH0139).

CRediT authorship contribution statement

Xianggao Zhu: Writing – original draft, Methodology, Formal analysis, Conceptualization. Hongfang Yu: Writing – original draft, Methodology, Formal analysis, Conceptualization. Hong Li: Writing – original draft, Methodology, Formal analysis, Conceptualization. Wei Zhang: Validation, Investigation, Data curation. Liping Sun: Validation, Investigation, Data curation. Ting Dou: Validation, Investigation, Data curation. Zhenfei Wang: Validation, Investigation, Data curation. Haiping Zhao: Writing – review & editing, Writing – original draft. Hao Yang: Writing – review & editing, Writing – original draft.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

Not applicable.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e27631.

Contributor Information

Haiping Zhao, Email: zhaohp2018@163.com.

Hao Yang, Email: haoyang050201@163.com.

List of abbreviations

HCC

Hepatocellular carcinoma

LncRNAs

Long-noncoding RNAs

LncRNA SNHG1

LncRNA small nucleolar RNA host gene 1

NSCLC

Non-small cell lung cancer

si-SHNG1

SNHG1 silencing

Appendix A. Supplementary data

The following are the supplementary data to this article:

figs1.

figs1

Open in a new tab

figs2.

figs2

Open in a new tab

References

  • 1.Anwanwan D., Singh S.K., Singh S., Saikam V., Singh R. Challenges in liver cancer and possible treatment approaches. Biochim. Biophys. Acta Rev. Canc. 2020;1873(1) doi: 10.1016/j.bbcan.2019.188314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. Ca - Cancer J. Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. [DOI] [PubMed] [Google Scholar]
  • 3.Li X., Ramadori P., Pfister D., Seehawer M., Zender L., Heikenwalder M. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat. Rev. Cancer. 2021;21(9):541–557. doi: 10.1038/s41568-021-00383-9. [DOI] [PubMed] [Google Scholar]
  • 4.Ringelhan M., Pfister D., O'connor T., Pikarsky E., Heikenwalder M. The immunology of hepatocellular carcinoma. Nat. Immunol. 2018;19(3):222–232. doi: 10.1038/s41590-018-0044-z. [DOI] [PubMed] [Google Scholar]
  • 5.Clark T., Maximin S., Meier J., Pokharel S., Bhargava P. Hepatocellular carcinoma: review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr. Probl. Diagn. Radiol. 2015;44(6):479–486. doi: 10.1067/j.cpradiol.2015.04.004. [DOI] [PubMed] [Google Scholar]
  • 6.Erratum Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca - Cancer J. Clin. 2020;70(4):313. doi: 10.3322/caac.21609. [DOI] [PubMed] [Google Scholar]
  • 7.Vogel A., Meyer T., Sapisochin G., Salem R., Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–1362. doi: 10.1016/S0140-6736(22)01200-4. [DOI] [PubMed] [Google Scholar]
  • 8.Santoni M., Rizzo A., Mollica V., et al. The impact of gender on the efficacy of immune checkpoint inhibitors in cancer patients: the MOUSEION-01 study. Crit. Rev. Oncol. Hematol. 2022;170 doi: 10.1016/j.critrevonc.2022.103596. [DOI] [PubMed] [Google Scholar]
  • 9.Rizzo A., Ricci A.D., Brandi G. Systemic adjuvant treatment in hepatocellular carcinoma: tempted to do something rather than nothing. Future Oncol. 2020;16(32):2587–2589. doi: 10.2217/fon-2020-0669. [DOI] [PubMed] [Google Scholar]
  • 10.Rizzo A., Ricci A.D., Brandi G. Trans-arterial chemoembolization plus systemic treatments for hepatocellular carcinoma: an update. J. Personalized Med. 2022;12(11) doi: 10.3390/jpm12111788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Di Federico A., Rizzo A., Carloni R., et al. Atezolizumab-bevacizumab plus Y-90 TARE for the treatment of hepatocellular carcinoma: preclinical rationale and ongoing clinical trials. Expert Opin Investig Drugs. 2022;31(4):361–369. doi: 10.1080/13543784.2022.2009455. [DOI] [PubMed] [Google Scholar]
  • 12.Allemani C., Matsuda T., Di Carlo V., et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–1075. doi: 10.1016/S0140-6736(17)33326-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Yoon J.H., Goo Y.J., Lim C.J., et al. Features of extrahepatic metastasis after radiofrequency ablation for hepatocellular carcinoma. World J. Gastroenterol. 2020;26(32):4833–4845. doi: 10.3748/wjg.v26.i32.4833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Luo H., Zhu G., Xu J., et al. HOTTIP lncRNA promotes hematopoietic stem cell self-renewal leading to AML-like disease in mice. Cancer Cell. 2019;36(6):645–659 e8. doi: 10.1016/j.ccell.2019.10.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Wang Z., Yang B., Zhang M., et al. lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell. 2018;33(4):706–720 e9. doi: 10.1016/j.ccell.2018.03.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Li Z., Lu X., Liu Y., et al. Gain of LINC00624 enhances liver cancer progression by disrupting the histone deacetylase 6/tripartite motif containing 28/zinc finger protein 354C corepressor complex. Hepatology. 2021;73(5):1764–1782. doi: 10.1002/hep.31530. [DOI] [PubMed] [Google Scholar]
  • 17.Coe E.A., Tan J.Y., Shapiro M., et al. The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor. PLoS Genet. 2019;15(12) doi: 10.1371/journal.pgen.1008501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Yan H., Bu P. Non-coding RNA in cancer. Essays Biochem. 2021;65(4):625–639. doi: 10.1042/EBC20200032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Zong S., Dai W., Guo X., Wang K. LncRNA-SNHG1 promotes macrophage M2-like polarization and contributes to breast cancer growth and metastasis. Aging (Albany NY) 2021;13(19):23169–23181. doi: 10.18632/aging.203609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Xu M., Chen X., Lin K., et al. The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol. Cancer. 2018;17(1):141. doi: 10.1186/s12943-018-0894-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Chen S., Guo W., Meng M., et al. LncRNA SNHG1 promotes the progression of pancreatic cancer by regulating FGFR1 expression via competitively binding to miR-497. Front. Oncol. 2022;12 doi: 10.3389/fonc.2022.813850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Li S.J., Wang L., Sun Z.X., Sun S.J., Gao J., Ma R.L. LncRNA SNHG1 promotes liver cancer development through inhibiting p53 expression via binding to DNMT1. Eur. Rev. Med. Pharmacol. Sci. 2019;23(7):2768–2776. doi: 10.26355/eurrev_201904_17550. [DOI] [PubMed] [Google Scholar]
  • 23.Ji Y.Y., Meng M., Miao Y. lncRNA SNHG1 promotes progression of cervical cancer through miR-195/NEK2 Axis. Cancer Manag. Res. 2020;12:11423–11433. doi: 10.2147/CMAR.S277064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Li W., Dong X., He C., et al. LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J. Exp. Clin. Cancer Res. 2019;38(1):183. doi: 10.1186/s13046-019-1177-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Qu A., Yang Q. LncRNA SNHG1 promotes cell progression and metastasis via sponging miR-377-3p in hepatocellular carcinoma. Neoplasma. 2020;67(3):557–566. doi: 10.4149/neo_2020_190705N593. [DOI] [PubMed] [Google Scholar]
  • 26.Wang J.Z., Fu X., Fang Z., et al. QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer. J. Mol. Cell Biol. 2021;13(5):347–360. doi: 10.1093/jmcb/mjaa063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Liang B., Jia C., Huang Y., et al. TPX2 level correlates with hepatocellular carcinoma cell proliferation, apoptosis, and EMT. Dig. Dis. Sci. 2015;60(8):2360–2372. doi: 10.1007/s10620-015-3730-9. [DOI] [PubMed] [Google Scholar]
  • 28.Wang Y., Yang H., Zhang G., et al. hsa-miR-7-5p suppresses proliferation, migration and promotes apoptosis in hepatocellular carcinoma cell lines by inhibiting SPC24 expression. Biochem. Biophys. Res. Commun. 2021;561:80–87. doi: 10.1016/j.bbrc.2021.05.020. [DOI] [PubMed] [Google Scholar]
  • 29.Wang J., Chen L., Qiang P. The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers. Cancer Cell Int. 2021;21(1):99. doi: 10.1186/s12935-021-01799-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Karanikola S.N., Krucken J., Ramunke S., et al. Development of a multiplex fluorescence immunological assay for the simultaneous detection of antibodies against Cooperia oncophora, Dictyocaulus viviparus and Fasciola hepatica in cattle. Parasit Vectors. 2015;8:335. doi: 10.1186/s13071-015-0924-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Yang J.D., Hainaut P., Gores G.J., Amadou A., Plymoth A., Roberts L.R. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 2019;16(10):589–604. doi: 10.1038/s41575-019-0186-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Huang Y. The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J. Cell Mol. Med. 2018;22(12):5768–5775. doi: 10.1111/jcmm.13866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Chen X., Song J., Wang X., Sun D., Liu Y., Jiang Y. LncRNA LINC00460: function and mechanism in human cancer. Thorac Cancer. 2022;13(1):3–14. doi: 10.1111/1759-7714.14238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Wang J.Y., Yang Y., Ma Y., et al. Potential regulatory role of lncRNA-miRNA-mRNA axis in osteosarcoma. Biomed. Pharmacother. 2020;121 doi: 10.1016/j.biopha.2019.109627. [DOI] [PubMed] [Google Scholar]
  • 35.Thin K.Z., Tu J.C., Raveendran S. Long non-coding SNHG1 in cancer. Clin. Chim. Acta. 2019;494:38–47. doi: 10.1016/j.cca.2019.03.002. [DOI] [PubMed] [Google Scholar]
  • 36.Wang Y., Yang F., Peng Q., Mei K., He H., Yang Q. Long non-coding RNA SNHG1 activates glycolysis to promote hepatocellular cancer progression through the miR-326/PKM2 axis. J. Gene Med. 2022;24(8):e3440. doi: 10.1002/jgm.3440. [DOI] [PubMed] [Google Scholar]
  • 37.Xiao H. MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2. Cell. Mol. Biol. Lett. 2019;24:60. doi: 10.1186/s11658-019-0188-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Christiansen J., Kolte A.M., Hansen Tv, Nielsen F.C. IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J. Mol. Endocrinol. 2009;43(5):187–195. doi: 10.1677/JME-09-0016. [DOI] [PubMed] [Google Scholar]
  • 39.Li X., Li Y., Lu H. [ARTICLE WITHDRAWN] miR-1193 suppresses proliferation and invasion of human breast cancer cells through directly targeting IGF2BP2. Oncol. Res. 2017;25(4):579–585. doi: 10.3727/97818823455816X14760504645779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Dai N., Ji F., Wright J., Minichiello L., Sadreyev R., Avruch J. IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1. Elife. 2017:6. doi: 10.7554/eLife.27155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Wu X.L., Lu R.Y., Wang L.K., et al. Long noncoding RNA HOTAIR silencing inhibits invasion and proliferation of human colon cancer LoVo cells via regulating IGF2BP2. J. Cell. Biochem. 2019;120(2):1221–1231. doi: 10.1002/jcb.27079. [DOI] [PubMed] [Google Scholar]
  • 42.Pu J., Wang J., Qin Z., et al. IGF2BP2 promotes liver cancer growth through an m6A-FEN1-dependent mechanism. Front. Oncol. 2020;10 doi: 10.3389/fonc.2020.578816. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data supporting the conclusions of this study were included in this article and supplementary materials. The data used and analyzed in the current study are available from the corresponding author upon a reasonable request.

Articles from Heliyon are provided here courtesy of Elsevier

RESOURCES