miR‐33a inhibits cell growth in renal cancer by downregulation of MDM4 expression

Abstract

Abstract Background MicroRNA‐33a (miR‐33a) plays the role of the tumor suppressor gene by regulating the expression level of downstream genes. However, the effects of miR‐33a in renal cell cancer (RCC) remain unknown. Our study was designed to investigate the expression level and potential function of miR‐33a in RCC. Methods RT‐qPCR was applied to measure the levels of miR‐33a in RCC tissues and cell lines. Western blotting and luciferase reporter assay were used to detect the relationship between miR‐33a and Mouse double minute 4 (MDM4) in RCC cells. CCK‐8 and flow cytometry were applied to detected cell viability and cell cycle. Animal models and TUNEL assay were applied to detect the effect of miR‐33a on the growth of RCC and cell apoptosis. Results We found that the levels of miR‐33a were significantly decreased in RCC tissues and cell lines. Moreover, the low expression of miR‐33a in RCC patients indicated a shorter overall survival (OS). Notably, MDM4 as a direct target of miR‐33a in RCC, the expression level of MDM4 was significantly increased in RCC cells group than the control group. Furthermore, miR‐33a overexpression significantly inhibited RCC cells growth than the control group, while the inhibitory effects of miR‐33a were reversed upon the overexpression of MDM4. Luciferase reporter assays showed that there was a direct interaction between miR‐33a and 3′ UTR of MDM4 mRNA. In vivo, tumor volumes and weight were significantly decreased in the transfected miR‐33a mimics group than the control group. Conclusion Taken together, our study indicates that miR‐33a inhibits RCC cell growth by targeting MDM4.

Keywords

• cell proliferation
• MDM4
• MiR‐33a
• renal cell cancer