MicroRNA-34C Plays A Role In Hepatocarcinogenesis By Targeting C-MET

BackgroundHepatocellular carcinoma is the sixth most common malignant tumor with a94%mortality, which is the third most common cause of cancer-related mortality worldwide.500,000people die each year from hepatocellular carcinoma. Its high incidence and mortality is a serious threat to the health of mankind. HBV and HCV infection was related with HCC, at present, the occurrence of HCC is a polygenic multi-stage process, in which relevant oncogene activation and tumor-suppressor gene inactivation play an important role, but the molecular pathogenesis of HCC is not entirely clear. As a result, the diagnosis and treatment of HCC was hindered and the prognosis of HCC was affected seriously.MicroRNAs are small RNA molecules composed of21～25nucleotides, regulate the expression of target genes at post-translation level, and are involved in various biological functions. MicroRNAs can suppress tumor development in the developing process of tumor, while they also can promote the development of tumor. Many studies have confirmed that microRNA-34expressed lowly in a variety of tumor, such as non-small cell lung cancer, breast cancer, glioma, and prostate cancer. The above studies suggest that microRNA-34family may perform the function of tumor suppressor genes in a wide variety of tumor development process. Recent study has found that microRNA-34family is the direct target of P53. The overexpression of microRNA-34can lead to cell apoptosis and cell cycle arrest. At present, the research of microRNA-34c is relatively rare, while it was reported that microRNA-34c is related to the occurrence and development of HCC.ObjectiveTo illustrate the role of microRNA-34c in HCC by targeting c-Met.Methods1.The expression of microRNA-34c in clinical hepatocellular carcinoma tissue and para-carcinoma tissue was detected by qPCR.2.The expression of c-Met in clinical hepatocellular carcinoma tissue and para-carcinoma tissue was detected by western blot.3.The expressions of c-Met mRNA and protein in HepG2.2.15cells transfected with microRNA-34c were detected by qPCR or western blot respectively.4.The expressions of P53protein in HepG2.2.15cells transfected with microRNA-34c or c-Met siRNA was detected by western blot.5.Xenograft nude mice model of liver cancer was established and the volume of tumors was measured.Results1.MicroRNA-34c expression was significantly decreased in the hepatocellular carcinoma tissue compared with para-carcinoma tissue. Nine of10hepatocellular carcinoma tissues showed that microRNA-34c was decreased in0.196～0.683fold, while another was increased in1.137fold.2.The expression of c-Met in hepatocellular carcinoma was decreased compared with para-carcinoma tissue. Seven of ten hepatocellular carcinoma tissues showed that expression of c-Met in hepatocellular carcinoma was lower than para-carcinoma tissue.3.MicroRNA-34c can inhibit c-Met expression in HepG2.2.15cells. Compared with control groups, microRNA-34c resulted in a0.356fold decrease of c-Met (P<0.01). This change was also noted at the translational level, as measured by western bolt. 4.Downregulation of c-Met enhanced P53activity (P<0.05).5.MicroRNA-34c inhibited the growth of liver cancer in xenograft nude mice model (P<0.05)ConclusionMicroRNA-34c expression is significantly decreased in the hepatocellular carcinoma tissue compared with para-carcinoma tissue, while the c-Met expression is inverse. MicroRNA-34c inhibits c-Met expression and enhance P53activity. MicroRNA-34c inhibits the tumor growth in xenograft nude mice model. Above all, microRNA-34c may play a role in suppressing the development of hepatocellular carcinoma by downregulating c-Met.