Table 1.
The Role of lncRNAs in Diabetes and Diabetic Complications
| Disease Name | LncRNA (Alias) | Dysfunction | Description | Location | PMID |
|---|---|---|---|---|---|
| Diabetes mellitus | CDKN2B-AS1 (ANRIL) | Mutation, Expression, Locus | Genetic variation in lncRNA genes causes disease and influences susceptibility. | 9p21.3 | 23791884, 20386740, 23104877, 20956613, 17463249, 20956613, 17463248, 18048406, 24624135 |
| CDKN2B-AS5 | Mutation | GWAS identified several variants in the intergenic region encompassing ANRIL to be associated with several diseases such as T5D. | N/A | 22928560 | |
| GAS5 (SNHG2) | Expression | LncRNA GAS5 levels are correlated to the prevalence of T2DM. | 1q25.1 | 26675493 | |
| H19 | Expression | Associated with increased birth weight; higher expression in T2D patients. | 11p15.5 | 17463249 | |
| IGF2-AS (PEG8) | Mutation | Association identified by GWAS. | 11p15.5 | 17554260 | |
| LINC01370 (HILNC25) | Regulation | Depletion of HI-LNC25, cell-specific lncRNA, down-regulated GLIS3 mRNA, thus exemplifying a gene regulatory function of islet lncRNAs. Finally, selected islet lncRNAs were dysregulated in type 2 diabetes or mapped to genetic loci underlying diabetes susceptibility. | 20q12 | 23040067 | |
| LINC00271 | Mutation | Association identified by GWAS. | 6q23.3 | 17668382 | |
| MALAT1 (NEAT2) | Expression | In addition, MALAT1, a conserved lncRNA, was significantly upregulated in an RF/6A cell model of hyperglycemia in the aqueous humor samples and fibrovascular membranes of diabetic patients. | 11q13.1 | 24436191 | |
| RNCR2 (MIAT, GOMAFU) | N/A | May affect β-cell mass. | 22q12.1 | 20486133 | |
| TUG1 | Regulation | A direct interaction between PGC-1α and Tug1 modulates mitochondrial bioenergetics in podocytes in the diabetic milieu. | 11 | 27760051 | |
| MEG3 (GTL2) | Locus, Expression | The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. | 14q32 | 19966805, 26845358, 26603935 | |
| MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. | |||||
| MEG3 may be a potential target and therapeutic strategy for diabetes. MEG3 knockdown aggravates retinal vessel dysfunction in vivo and regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. | |||||
| NEAT1 | Regulation | Regulates mTOR signaling pathway. | 11q13.1 | 28643459 | |
| NONHSAG011351 | Regulation | ERBB3, whose locus associated lncRNA (NONHSAG011351) was expressed in human islets, may constitute novel targets to prevent β-cell destruction in T1D. | 12q24.13 | 26450151 | |
| PDZRN3-AS1 | Mutation | SNP rs11128347 (C>G) in PDZRN3 is associated with African Americans with type 2 diabetes. | 3p13 | 21546767 | |
| PINK1-AS | Expression | PINK1 is induced by PTEN, which is an important inhibitor of insulin signaling. PINK1 depletion has been associated with diabetes status, impaired glucose uptake in neuronal cell lines, and mitochondrial gene expression in adipocytes, raising the possibility that disruption to naPINK1 may impact glucose metabolism. | 1p36.12 | 22817756 | |
| PLUTO (PDX1-AS1) | N/A | Regulates PDX1 expression. | 13q12.2 | 28041957 | |
| PVT1 (onco-lncRNA-100) | Mutation | There is an association between variants (rs2720709, A>G) in the plasmacytoma variant translocation 1 gene (PVT1) and end-stage renal disease (ESRD) attributed to both type 1 and type 2 diabetes. Identification of PVT1 (rs2720709, A>G) as a candidate gene for end-stage renal disease in type 2 diabetes using a pooling-based genome-wide single nucleotide polymorphism association study. |
8q24.21 | 21526116, 17395743 | |
| RNCR3 (LINC00599) | Locus | RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. | 8p23.1 | 27616193 | |
| Diabetic retinopathy | MALAT1 (NEAT2) | Regulation Expression |
MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. MALAT1 down-regulation could ameliorate DR by functioning as a competing endogenous RNA in regulating VEGF levels through miR-150-5p. MALAT1 may become a potential therapeutic target for the prognosis, diagnosis, and treatment of DR. associated with markers of visual and retinal vessel function. Activates inflammatory pathway via TNF-α and IL-6. | 11q13.1 | 25356875, 24436191 |
| RNCR2 (MIAT, GOMAFU) | Regulation | MIAT knockdown could repress TNF-α-induced abnormal proliferation and migration of HLECs, by acting as a ceRNA. Attenuates retinal vessel impairment and vascular leakage and formed a feedback loop with Akt and miR-150-5p. NF-κB activation | 22q12.1 | 27043545, 29074557 | |
| MEG3 | N/A | Modulates angiogenesis by PI3K/Akt | 14q32.2 | 26845358 | |
| CDKN2B-AS1 (ANRIL) | N/A | Increases retinal microvascular permeability in vivo Increases VEGF mediated by PRC2 complex and p300 |
9p21.3 | 28122089, 23813974 | |
| RNCR3(LINC00599) | N/A | Increases cell viability and proliferation, promotes EC migration and tube formation in vitro Aggravates retinal cell apoptosis, visual function, and microvascular leakage in vivo Related to the release of several cytokines |
8p23.1 | 21857657, 27253412 | |
| BDNF-AS | N/A | Increases cell apoptosis. Cause early neurodegeneration |
11p14.1 | 23271640, 26004392 | |
| SOX2OT | N/A | Mediates glucose-induced retinal injury. Antioxidative via regulation of NRF2/HO-1 signaling activity Promotes neurodegeneration |
3q26.33 | 27193103, 29074557, 18846214 | |
| Diabetic cardiomyopathy | H19 (WT2) | Regulation | LncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. | 11p15.5 | 27796346 |
| MALAT1 (NEAT2) | Regulation | Involvement of long non-coding RNA MALAT1 in the pathogenesis of diabetic cardiomyopathy. | 11q13.1 | 26476026 | |
| Diabetic nephropathy | CYP4B1-PS1 | Regulation | A novel long non-coding RNA CYP4B1 PS1-001 regulates proliferation and fibrosis in diabetic nephropathy. may regulate proliferation and fibrosis in mesangial cells [52 | N/A | 26923441 |
| ENSMUST00000147869 | Regulation | Long non-coding RNA ENSMUST00000147869 protects mesangial cells from proliferation and fibrosis induced by diabetic nephropathy. | N/A | 27083175 | |
| PVT1 (onco-lncRNA-100) | Expression Interaction Regulation |
Variants in the plasmacytoma variant translocation gene were strongly associated with DKD in the Pima Indians, a group with the highest prevalence of type 2 diabetes in the world. PVT1 may mediate the development and progression of diabetic nephropathy through mechanisms involving ECM accumulation. Role of MicroRNA 1207–5P and Its Host Gene, the Long Noncoding RNA Pvt1, as Mediators of Extracellular Matrix Accumulation in the Kidney. |
8q24.21 | 27503944, 21526116, 24204837, 24204837 | |
| RNCR2 (MIAT, GOMAFU) | Regulation | Mediates high glucose-induced renal tubular epithelial injury. | 22q12.1 | 26551455 |
Note: The Bold names were selected in this study. Data source: LncRNADisease database (http://www.cuilab.cn) and literature search.