MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4.

2015 
MicroRNAs (miRNAs) play a crucial role in cancer development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor prognostic factor for HCC patient overall and disease-free survival rate. A significant correlation was observed between miR-194 reduction and unfavourable variables including tumor size (P = 0.0315), histologic grade (P = 0.0038), TNM stage (P = 0.0083), intrahepatic metastasis (P = 0.0184). Overexpression of miR-194 in HCC cell lines HepG2 and Hep3B inhibited cell proliferation by blocking G1-S transition and inducing apoptosis. Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines. Further studies demonstrated that miR-194 regulated the progression of HCC through directly inhibiting the expression of MAP4K4 and the restoration of MAP4K4 expression reversed the inhibitory effects of miR-194 on HCC cell proliferation. Together, our findings indicate that miR-194 may serve as a valuable prognostic marker and promising interventional therapeutic target for HCC.
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