MicroRNA-148a inhibits hepatocellular carcinoma cell invasion by targeting sphingosine-1-phosphate receptor 1

Abstract

microRNA (miR)-148a has been shown to act as an important suppressor in numerous human malignancies and is markedly downregulated in hepatocellular carcinoma; however, the role of miR-148a in the regulation of hepatocellular carcinoma cell invasion, as well as the underlying mechanism, has never been studied. In the present study, the expression level of miR-148a was found to be significantly decreased in hepatocellular carcinoma tissues and HepG2 cells when compared with that in the normal adjacent tissues. Furthermore, a novel target of miR-148a was found, sphingosine-1-phosphate receptor 1 (S1PR1), whose expression was negatively regulated by miR-148a at a post-transcriptional level in hepatocellular carcinoma HepG2 cells. Upregulation of miR-148a by transfection with miR-148a mimics notably suppressed HepG2 cell invasion, similar to the effect of the SIPR1 downregulation induced by SIPR1-specific small interfering RNA, while the restoration of S1PR1 expression reversed the inhibitory effect of miR-148a upregulation on HepG2 cell invasion. Accordingly, the current study suggests that miR-148a plays an inhibitory role in the regulation of hepatocellular carcinoma cell invasion by directly targeting S1PR1.