MiR-488 suppresses cell proliferation and invasion by targeting ADAM9 and lncRNA HULC in hepatocellular carcinoma

Am J Cancer Res. 2017 Oct 1;7(10):2070-2080. eCollection 2017.

Abstract

MicroRNAs (miRNAs) have been identified as regulators of tumor proliferation, invasion, and metastasis in hepatocellular carcinoma (HCC). In the current study, we determined the clinical significance and biological role of miR-488 in HCC. Our results demonstrated that the expression of miR-488 was notably downregulated in HCC tissues compared with paired adjacent normal tissues. Lower miR-488 expression was positively associated with tumor size, vascular invasion, and shorter overall survival (OS) in HCC patients. Furthermore, gain-and-lost function assays showed that upregulation of miR-488 significantly inhibited cell proliferation, colony formation, cell invasion, and the epithelial-to-mesenchymal transition (EMT) process. We showed that ADAM9 served as a direct target for miR-488 and mediated lower miR-488 expression, thus inducing cell proliferation and invasion in HCC. Moreover, we found that lncRNA HULC is a target of miR-488 in HCC cells and miR-488 inhibited the expression of HULC by sponging to HULC in HCC. Thus, our results suggest that miR-488 functions as a tumor suppressor in HCC and may be a potential target for HCC treatment.

Keywords: ADAM9; HULC; Hepatocellular carcinoma; cell proliferation; miR-488.