Downregulation of miR-7 upregulates Cullin 5 (CUL5) to facilitate G1/S transition in human hepatocellular carcinoma cells

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that participate in the regulation of gene expression. In this study, we demonstrate that miR-7 was downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent non-tumor tissue. Over-expression of miR-7 in QGY-7703 and HepG2 cell lines inhibited colony formation and induced G1/S phase arrest, whereas knockdown of miR-7 produced the opposite phenotype. A tumor suppressor gene, CUL5, was identified as a direct target of miR-7, and CUL-5 is upregulated upon the binding of miR-7 to its 3'UTR. Furthermore, suppression of CUL5 also suppressed cell colony formation and induced cell cycle arrest. Ectopic expression of CUL5 abrogated the effects of miR-7 inhibition on QGY-7703 and HepG2 cell lines. These results indicate that miR-7 suppresses colony formation and causes cell cycle arrest via upregulation of CUL5, and it may function as a tumor suppressor in HCC.

Keywords: CUL5; cell cycle; hepatocellular carcinoma; miR-7; miRNA.