MicroRNA-۲۰۵ inhibits renal cells apoptosis via targeting CMTM۴

Objective(s):MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microRNA ۲۰۵ (miR-۲۰۵) in cisplatin-induced renal cell apoptosis and explored the molecular mechanisms. Materials and Methods:The chronic interstitial nephropathy rat model was induced, and the miRNA expression profile in the kidney cells from rats with CKD was screened. Cisplatin-induced apoptosis in normal renal HK-۲ cells was evaluated using flow cytometry, and regulation of miR-۲۰۵ on target gene was validated using luciferase assay, western blot and real time PCR assays. Results: We found that miR-۲۰۵ expression was significantly decreased in the cells from kidney of CKD rat (P<۰.۰۱). Our data showed that when miR-۲۰۵ was overexpressed or silenced using the mimic or inhibitor, the percentages of apoptotic cells were suppressed or increased significantly (P<۰.۰۵), respectively. Moreover, we have identified CMTM۴ gene, which is involved in cell proliferation and apoptosis, as a novel target for miR-۲۰۵. In addition, miR-۲۰۵ could inhibit apoptosis by binding to the ۳’UTR of CMTM۴ mRNA and inhibiting its transcriptional activity. Conclusion: This study elucidated that miR-۲۰۵ plays an important role in the regulation of apoptosis in renal cells, suggesting a potential therapeutic target to hinder CKD development.

Keywords:

Apoptosis , chronic kidney disease , CMTM۴ , microRNA ۲۰۵