MiR-501-5p regulates CYLD expression and promotes cell proliferation in human hepatocellular carcinoma.

Abstract

Previous studies have shown that the micro-ribonucleic acid miR-501-5p is upregulated in hepatocellular carcinoma cells and tissues with high hepatitis B virus replication, and that miR-501 overexpression significantly promotes hepatitis B virus replication. We further analysed a published microarray-based high-throughput dataset (NCBI/GEO/GSE36915) and found that miR-501-5p was upregulated in hepatocellular carcinoma tumour tissues. We therefore investigated the possible function of miR-501-5p during the development of hepatocellular carcinoma. Expression of miR-501-5p in human hepatocellular carcinoma specimens and cell lines was assessed, using real-time polymerase chain reaction. Luciferase reporter assays were used to confirm CYLD as a target of miR-501-5p. The effect of miR-501-5p on cell proliferation was confirmed, using tetrazolium and colony formation assays. Gene and protein expression were examined, using real-time polymerase chain reaction and western blotting, respectively. MiR-501-5p was upregulated in hepatocellular carcinoma specimens and cell lines, and directly targeted the 3' untranslated region of CYLD. MiR-501-5p upregulation corresponded with a downregulation of CYLD in the same tissues and cell lines, and overexpression of MiR-501-5p decreased CYLD expression, increased expression of cyclin D1 and c-myc and promoted the proliferation of hepatocellular carcinoma cells in vitro. This study suggests that miR-501-5p may play an important role in the development of hepatocellular carcinoma by promoting cell proliferation, and indicates that miR-501-5p may represent a novel therapeutic target for hepatocellular carcinoma.