Abstract
BackgroundLong non-coding RNAs (lncRNAs) have been reported to play vital roles in diabetic nephropathy (DN). The aim of this study was to explore the function of mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in DN.MethodsDN cell models were established using high glucose (HG) treatment in human glomerular mesangial cells (HGMC) and human renal glomerular endothelial cells (HRGEC). The expression levels of KCNQ1OT1, microRNA-93-5p (miR-93-5p), and Rho associated coiled-coil containing protein kinase 2 (ROCK2) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. ROCK2 and apoptosis/fibrosis-related protein levels were examined by western blot. The predicted interaction between miR-93-5p and KCNQ1OT1 or ROCK2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.ResultsKCNQ1OT1 was upregulated in DN patients and DN cell models. KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN cell models. MiR-93-5p was a direct target of KCNQ1OT1, and miR-93-5p inhibition restored the KCNQ1OT1 knockdown-mediated effects on cell proliferation, fibrosis and apoptosis in DN cell models. In addition, ROCK2 was identified as a target of miR-93-5p, and miR-93-5p overexpression suppressed cell proliferation and fibrosis and accelerated apoptosis by targeting ROCK2 in DN cell models. Moreover, KCNQ1OT1 regulated ROCK2 expression by binding to miR-93-5p.ConclusionKCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN by regulating miR-93-5p/ROCK2 axis, providing potential value for the treatment of DN.
Highlights
Diabetic nephropathy (DN), a serious complication of diabetes mellitus, has become the primary cause of endstage renal disease (ESRD) and mortality in people with diabetes [1]
KCNQ1OT1 was upregulated and miR‐93‐5p was downregulated in diabetic nephropathy (DN) Firstly, KCNQ1OT1 and miR-93-5p levels in the serum of DN patients were determined by quantitative real-time polymerase chain reaction (qRT-PCR)
The data showed that the expression of KCNQ1OT1 was increased and the expression of miR-93-5p was decreased in the serum of DN patients compared with that in normal group (Fig. 1A and B)
Summary
Diabetic nephropathy (DN), a serious complication of diabetes mellitus, has become the primary cause of endstage renal disease (ESRD) and mortality in people with diabetes [1]. Increasing studies have shown that lncRNAs can participate in diverse pathological and physiological processes [10]. Some lncRNAs have been confirmed to play critical regulatory roles in DN. LncRNA LINC00968 promoted mesangial cell proliferation and fibrosis in DN [11]. LncRNA NEAT1 overexpression accelerated mesangial cell proliferation and fibrosis as well as restrained apoptosis in DN [12]. As for lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), it has been shown to participate in DN progression and its expression was upregulated in DN [14]. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in diabetic nephropathy (DN). The aim of this study was to explore the function of mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in DN
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