MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma.

Abstract

MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. Recently, microRNA-373 (miR-373) has been found to function as an oncogene in testicular germ cell tumors. In our study, we found that miR-373 is upregulated in human hepatocellular carcinoma (HCC) tissues as compared with adjacent normal tissues, and promotes the proliferation of the HCC cell lines HepG2 and QGY-7703 by regulating the transition between G(1)-phase and S-phase. The gene encoding the protein phosphatase 6 catalytic subunit (PPP6C ), a negative cell cycle regulator, was identified as a direct target gene of miR-373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR-373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR-373 in HepG2 cells. These results indicate that miR-373 plays an important role in the pathogenesis of HCC, and may be a new biomarker in HCC. Our results demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may explain why the expression of miR-373 can promote HCC cell proliferation.