Down-regulation of MAP2K1 by miR-539 inhibits hepatocarcinoma progression

Liver cancer has been considered as one of the major leading causes of cancer-related mortality. The incidence of liver cancer tends to increase in less developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs) play crucial roles in the modulation of tumor growth and progression. Whereas, the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well established. In our present study, we sought to explore biological role of miR-539 in HCC progression. qRT-PCR was utilized to evaluate the expression level of miR-539. Immunoblotting analysis, qRT-PCR and luciferase reporter assays were used for the identification of the potential target of miR-539. Proliferation, migration and invasion assays and flow cytometric were performed to assess the biological functional role of miR-539. The molecular signaling pathways related to the integration of miR-539 were also evaluated. MiR-539 was reduced in human HCC. Mitogen-activated protein kinase 1, also known as MAP2K1 was verified as the target of miR-539. Overexpression of miR-539 inhibited migration, invasion and cell proliferation, while apoptosis rate was increased. Knockdown or overexpression of MAP2K1 in HCC cell transfected with ag-miR-539 or in-miR-539 indicated that miR-539 suppresses the progression of HCC by directly targeting and regulating MAP2K1. Our results reveal that miR-539 might be a tumor suppressor in HCC, supporting a potential target for advanced therapeutic strategy for this disease.