MiR-124 retards bladder cancer growth by directly targeting CDK4.

MicroRNAs (miRNAs) are a class of non-coding small RNAs that act as negative regulators of gene expression by binding to the 3'-untranslated region (3'UTR) of target mRNAs. In order to investigate the physiological role of miR-124 in bladder cancer, target genes of miR-124 were predicted by the TargetScan software, and cyclin-dependent kinase (CDK4), which has been implicated as a regulator of cell cycle, was chosen for further study. MiR-124 could significantly repress CDK4 expression by targeting its binding site in the 3'UTR of CDK4 in vitro. In both bladder cancer cell lines and tissues, the expression of miR-124 was significantly down-regulated, while CDK4 expression was up-regulated. Ectopic expression of miR-124 in transplanted HT1197 cells resulted in the retardation of tumor growth in mouse tumor xenografts. And the expression of miR-124 and CDK4 showed an obvious inverse correlation in these xenograft tissues, which was also observed in human bladder cancer tissue samples. Taken together, our results strongly suggest that miR-124 can arrest cell cycle and restrain the growth of bladder cancer by targeting CDK4 directly.