MicroRNA-205 inhibits renal cells apoptosis via targeting CMTM4

Document Type : Original Article


Department of Internal Medicine, Shengli Oilfield Central Hospital, Dongying City, Shandong Province, 257034, P. R. China


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 205 (miR-205) 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-2 cells was evaluated using flow cytometry, and regulation of miR-205 on target gene was validated using luciferase assay, western blot and real time PCR assays.
Results: We found that miR-205 expression was significantly decreased in the cells from kidney of CKD rat (P<0.01). Our data showed that when miR-205 was overexpressed or silenced using the mimic or inhibitor, the percentages of apoptotic cells were suppressed or increased significantly (P<0.05), respectively. Moreover, we have identified CMTM4 gene, which is involved in cell proliferation and apoptosis, as a novel target for miR-205. In addition, miR-205 could inhibit apoptosis by binding to the 3’UTR of CMTM4 mRNA and inhibiting its transcriptional activity.
Conclusion: This study elucidated that miR-205 plays an important role in the regulation of apoptosis in renal cells, suggesting a potential therapeutic target to hinder CKD development.


1. Duffield JS, Grafals M, Portilla D. MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models. Drug Discov Today Dis Models 2013; 10:e127-e35.
2. Ishii Y, Sawada T, Kubota K, Fuchinoue S, Teraoka S, Shimizu A. Injury and progressive loss of peritubular capillaries in the development of chronic allograft nephropathy. Kidney Int 2005; 67:321-332.
3. Lee R, Feinbaum R, Ambros V. A short history of a short RNA. Cell 2004; 116:S89-92, 1 p following S6.
4. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456:980-984.
5. Majid S, Saini S, Dar AA, Hirata H, Shahryari V, Tanaka Y, et al. MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Res 2011; 71:2611-2621.
6. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, et al. Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 2007; 67:11612-11620.
7. Qin AY, Zhang XW, Liu L, Yu JP, Li H, Wang SZ, et al. MiR-205 in cancer: an angel or a devil? Eur J Cell Biol 2013; 92:54-60.
8. Plate M, Li T, Wang Y, Mo X, Zhang Y, Ma D, et al. Identification and characterization of CMTM4, a novel gene with inhibitory effects on HeLa cell growth through Inducing G2/M phase accumulation. Mol cells 2010; 29:355-361.
9. Vaziri ND, Liu SM, Lau WL, Khazaeli M, Nazertehrani S, Farzaneh SH, et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One 2014; 9:e114881.
10. Inami Y, Hamada C, Seto T, Hotta Y, Aruga S, Inuma J, et al. Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats. Int J Nephrol 2014; 2014:164125.
11. Nguy L, Johansson ME, Grimberg E, Lundgren J, Teerlink T, Carlstrom M, et al. Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness. Am J Physiol Regul Integr Comp Physiol 2013; 304:R744-752.
12. Dirks J, Remuzzi G, Horton S, Schieppati A, Rizvi SAH. Diseases of the Kidney and the Urinary System. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, et al. editors. Disease Control Priorities in Developing Countries. 2nd ed. Washington (DC):2006.
13. Hostetter TH. Chronic kidney disease predicts cardiovascular disease. N Engl J Med 2004; 351:1344-1346.
14. National Kidney F. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J kidney Dis 2002; 39:S1-266.
15. Chung AC, Lan HY. MicroRNAs in renal fibrosis. Front Physiol 2015; 6:50.
16. Patnaik S, Mallick R, Kannisto E, Sharma R, Bshara W, Yendamuri S, et al. MiR-205 and MiR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies. J Thorac Oncol 2015; 10:446-453.
17. Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, et al. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res 2015; 75:1322-1331.
18. Li J, Li L, Li Z, Gong G, Chen P, Liu H, et al. The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion. Gynecol Oncol 2015; 137:125-133.
19. Zhang P, Wang L, Rodriguez-Aguayo C, Yuan Y, Debeb BG, Chen D, et al. miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13. Nat Commun 2014; 5:5671.
20. Lei L, Huang Y, Gong W. miR-205 promotes the growth, metastasis and chemoresistance of NSCLC cells by targeting PTEN. Oncol Rep 2013; 30:2897-2902.
21. Alla V, Kowtharapu BS, Engelmann D, Emmrich S, Schmitz U, Steder M, et al. E2F1 confers anticancer drug resistance by targeting ABC transporter family members and Bcl-2 via the p73/DNp73-miR-205 circuitry. Cell Cycle 2012; 11:3067-3078.
22. Kittler R, Putz G, Pelletier L, Poser I, Heninger AK, Drechsel D, et al. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 2004; 432:1036-1040.
23. Trionfini P, Benigni A, Remuzzi G. MicroRNAs in kidney physiology and disease. Nat Rev Nephrol 2015; 11:23-33.