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

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.