MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is downregulated in hepatocellular carcinoma

Abstract

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that regulate physiological and pathological processes by suppressing target gene expression. Altered expression of miR-30a-3p has been demonstrated in several cancers. However, little about how miR-30a-3p functions in these cancers has been reported, and the role of miR-30a-3p in hepatocellular carcinoma (HCC) is unknown. The purpose of this study was to identify the role and underlying molecular mechanism of action of miR-30a-3p in HCC. MethodsA total of 110 HCC patients, primarily treated by surgical removal of tumors, were involved in the study. HCC cell line Bel-7402 was selected to characterize the function of miR-30a-3p in vitro. ResultsOur results showed that in 83.6% of the 110 HCC patients, expression of miR-30a-3p was significantly downregulated (P < 0.0001) in tumors compared to adjacent normal tissues. In a clinicopathological correlation analysis, downregulation of miR-30a-3p correlated with a significantly higher incidence of portal vein tumor thrombus (PVTT, P = 0.009). Moreover, miR-30a-3p markedly inhibited the invasion and migration of Bel-7402 HCC cells in vitro. Furthermore, miR-30a-3p overexpression had an inhibitory effect on cell proliferation, induced apoptosis and increased arrest of cells in the S phase. We further demonstrated that miR-30a-3p regulates HCC cell function by a mechanism involving reduced vimentin and MMP3 expression and restoration of E-cadherin expression. Conclusionsour data suggest that miR-30a-3p is downregulated in HCC and acts as a tumor suppressor in vitro. Regulation of vimentin, E-cadherin and MMP3 by miR-30a-3p suggests a useful therapeutic strategy for tumors with reduced miR-30a-3p expression.