Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression

Ge, Xin; Xu, Bojin; Xu, Wenwei; Xia, Lili; Xu, Zhongqin; Shen, Lisha; Peng, Wenfang; Huang, Shan

doi:10.18632/aging.102249

Cited by 74 publications

(48 citation statements)

References 30 publications

(33 reference statements)

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“…Therefore, we supposed that GAS regulated the expression of INSR, PIK3R1 and IRS1 through competitively interacting miR-29a-3p, miR-96-3p, and miR-208a-3p, but we cannot exclude other mechanisms play a role in this regulation, such as epigenetic mechanism (Sun et al, 2017). MiR-452-5p and miR-221-3p are two valid targets of GAS5 in renal tubular cells and mesangial cells, respectively, and both of them are involved in diabetic nephropathy (Ge et al, 2019;Xie et al, 2019). However, the levels of miR-452-5p and miR-221-3p were comparable between high GAS5 group and low GAS5 group.…”

Section: Discussionmentioning

confidence: 89%

“…LncRNA, as a competitive endogenous RNA (ceRNA), binds to miRNA and acts as a miRNA sponge, thereby reducing the activity of miRNA and indirectly up-regulating the expression of miRNA-related target genes (Goustin et al, 2019). It has been reported that GAS5 targets to miR-452-5p and miR-221-3p in renal tubular cells and mesangial cells, which are involved in diabetic nephropathy (Ge et al, 2019;Xie et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Long Non-coding RNA GAS5 Maintains Insulin Secretion by Regulating Multiple miRNAs in INS-1 832/13 Cells

Luo

Guo

et al. 2020

Front. Mol. Biosci.

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Type-2 diabetes mellitus (T2DM) is a complex disease characterized by reduced pancreatic islets β-cell mass and impaired insulin release from these cells. Non-coding RNAs, including microRNAs (miRNA) and long non-coding RNAs (lncRNAs), play a role in the progression of T2DM. Decreased serum lncRNA GAS5 levels were reported to be associated with T2DM. However, the role of GAS5 in regulating islet cell functions remain unknown. In this study, we found that the serum levels of GAS5 were significantly lower in patients with T2DM compared with healthy control subjects, and the low serum GAS5 levels were associated with high levels of HbAlc and fasting glucose in patients with T2DM. In addition, we found that serum GAS5 levels were negatively correlated with the serum levels of miR-29a-3p, miR-96-3p, and miR-208a-3p in patients with T2DM. Consequently, using INS-1 832/13 rat β-cell line, we found that overexpression of GAS5 by lentivirus infection increased glucose-stimulated insulin secretion and insulin content compared with negative control, whereas knockdown of GAS5 expression reduced both them. Moreover, GAS5 interacted with miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells, as judged by pull-down assay and dual luciferase reporter assay. GAS5 overexpression caused the decrease in expression of miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells and conversely caused the increase in expression of insulin receptor, insulin receptor substrate, and phosphoinositide-3-kinase regulatory subunit 1. Thus, these results reveal a novel mechanism whereby GAS5 is involved in maintaining insulin secretion and may represent a novel therapeutic target for T2DM.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA GAS5 Maintains Insulin Secretion by Regulating Multiple miRNAs in INS-1 832/13 Cells

Luo

Guo

et al. 2020

Front. Mol. Biosci.

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“…For instance, lncRNA Malat1 contributed to berberine-mediated suppression of HMGB1 to promote poststroke inflammation by sponging miR-181c-5p [33]. Long noncoding RNA GAS5 was proved to limit cell proliferation and fibrosis by sponging miR-221 and regulating SIRT1 levels in diabetic nephropathy [34]. Recently, a few lncRNAs including SOX2-OT were reported to be upregulated in MI [19,35].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

Yang

Lin

2020

Cardiovascular Therapeutics

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Background. Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods. Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results. We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions. Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

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“…The lncRNAs are a newly recognized mechanism for gene regulation and are being explored as potential therapeutic targets in a variety of diseases (Li et al, 2018;Pecero et al, 2019;Wang et al, 2020), including diabetic nephropathy (Ge et al, 2019;Yang et al, 2019). A nucleic acid-based approach could allow greater specificity than pharmacological compounds, reducing side effects and allowing tissue-specific delivery (Sharma and Watts, 2015;Ku et al, 2016).…”

Section: Figure 8 | Ko Of Edn1-as Regulatory Elements Results In Incrmentioning

confidence: 99%

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

et al. 2020

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Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressurelowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, EDN1. Here we report a long, non-coding RNA (lncRNA) that appears to be antisense to the EDN1 gene, called EDN1-AS. Because EDN1-AS represents a potential novel mechanism to regulate ET-1 expression, we examined the regulation of EDN1-AS expression and action. A putative glucocorticoid receptor response (GR) element upstream of the predicted EDN1-AS transcription start site was identified using the ENCODE database and the UCSC genome browser. Two homozygous deletion clones of the element were generated using CRISPR/Cas9. This deletion resulted in a significant increase in the expression of EDN1-AS, which was associated with increased secretion of ET-1 peptide from HK-2 cells (two-fold increase in KO cells vs. CNTL, n = 7, P < 0.05). Phenotypic characterization of these CRISPR clones revealed a difference in cell growth rates. Using a standard growth assay, we determined that the KO1 clone exhibited a three-fold increase in growth over 8 days compared to control cells (n = 4, P < 0.01) and the KO2 clone exhibited a two-fold increase (n = 4, P < 0.01). These results support a role for EDN1-AS as a novel regulatory mechanism of ET-1 expression and cellular proliferation.

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Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression

Cited by 74 publications

References 30 publications

Long Non-coding RNA GAS5 Maintains Insulin Secretion by Regulating Multiple miRNAs in INS-1 832/13 Cells

Long Non-coding RNA GAS5 Maintains Insulin Secretion by Regulating Multiple miRNAs in INS-1 832/13 Cells

Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells

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