miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP

Abstract

MicroRNAs (miRNAs) regulate a variety of development and physiologic processes, and play prominent roles in the initiation and progression of human cancers including hepatocellular carcinoma (HCC). MiR-23c is recently emerging as a cancer-associated miRNA, while its expression status and functional role in HCC are unrevealed yet. Here, we found that miR-23c underexpression was associated with the tumorigenesis of HCC based on TCGA data. qRT-PCR analysis revealed that miR-23c expression was reduced in HCC tissues and cell lines. Clinical analysis indicated that low miR-23c expression was correlated with large tumor size, high tumor grade, advanced tumor stage and poor survival of HCC patients. Our in vitro experiments found that overexpression of miR-23c inhibited cell proliferation and induced apoptosis of HCC cells. While miR-23c knockdown led to HCC cell growth arrest and apoptosis. Additionally, miR-23c overexpression repressed tumor growth of HCC in vivo. Mechanistically, erbb2 interacting protein (ERBB2IP) was identified as a direct target of miR-23c in HCC cells. miR-23c suppressed ERBB2IP expression in HCC cells and inversely correlated with ERBB2IP mRNA expression in HCC tissues. Notably, ERBB2IP silencing restrained HCC cell proliferation and induced apoptosis. ERBB2IP restoration reversed the inhibitory effects of miR-23c on HCC cell growth. In conclusion, our observations suggested that miR-23c inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP. Targeting miR-23c might open a new avenue for HCC treatment.

Keywords: Apoptosis; ERR2IP; Hepatocellular carcinoma; Tumor growth; microRNA-23c.