MicroRNA-30a suppresses tumor progression by blocking Ras/Raf/MEK/ERK signaling pathway in hepatocellular carcinoma

Abstract

Emerging reports suggest microRNAs (miRNAs) play a vital role in the progression of malignant tumors. MiR-30a is downregulated in a variety of cancers and acts as a tumor suppressing gene. However, the molecular mechanisms of miRNA-30a in hepatocellular carcinoma (HCC) are still unclear. Hereby, in this study, we detected that miR-30a expression was significantly down-regulated in both HCC tissues compared with adjacent non-cancerous liver tissues, and we also observed that miR-30a expression was lower in HCC cell lines than that of normal controls. By overexpression of miRNA-30a, we evaluated cell growth with CCK-8 assay and cell apoptosis by flow cytometry. The function of miR-30a on cellular migration in HCC cells was assessed. The potential target genes of miR-30a were analyzed with luciferase activity assay. Our data displayed that miR-30a mimic markedly inhibited HCC cell growth, induced cell apoptosis, and upregulated the expression of apoptotic proteins in HepG2 and MHCC976L cells. We also found that upregulation of miR-30a significantly inhibited HCC cells migration and invasion. Bioinformatics analysis revealed K-Ras was a regulative target gene of miR-30a, and further dual luciferase reporter assay showed that miR-30a directly binds to the 3'-untranslated region (3'-UTR) of K-Ras mRNA. Furthermore, we found that in HepG2 and MHCC97L cancer cells, miR-30a overexpression completely blocked the K-Ras/c-Raf/MEK/ERK pathway activation. Overall, these findings demonstrated that miR-30a might play a certain role in the cell growth, apoptosis and metastasis of HCC cells, partially via regulating K-Ras/c-Raf/MEK/ERK signaling pathway, potentially, it is therefore a candidate targeting biomarker for HCC therapy.