Identification of microRNA-124 in regulation of Hepatocellular carcinoma through BIRC3 and the NF-κB pathway

鉴定 microRNA-124 通过 BIRC3 和 NF-κB 通路调控肝细胞癌

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作者:Jia Cao, Jing Qiu, Xi Wang, ZhenHui Lu, Danni Wang, HuiMin Feng, XiaoHan Li, QiaoQiao Liu, HuaZheng Pan, XueBo Han, Jun Wei, ShiHai Liu, LiBin Wang

Abstract

MicroRNAs (miRNAs) being proved to be involved in the carcinogenesis of numerous tumors. MicroRNA-124 (miR-124), identified as a tumor suppressor, has been demonstrated to exert pivotal roles in multiple processes of tumorigenesis. The present study demonstrated that miR-124 was low-expressed in human hepatocellular carcinoma (HCC) tissues and cell lines. In addition, overexpression of miR-124 through infected with miR-124 lentivirus inhibited the proliferation and migration of HCC in vitro and tumorigenesis in vivo, whereas inhibition of miR-124 expression can reverse the process. Moreover, Baculoviral IAP Repeat Containing 3 (BIRC3) was identified as a target gene of miR-124. The BIRC3 mRNA expression was increased in HCC tissues and negatively correlated with miR-124 expression. Knockdown of BIRC3 recovered the miR-124-induced inhibiting effect on HCC progression. Furthermore, we found that up-regulation of miR-124 significantly inhibited p-P65, p-IκBα and c-Myc proteins expression. However, the effect of miR-124 up-regulation on HCC development was partly reversed by BIRC3 restoration. In conclusion, our data proved that miR-124 inhibits the proliferation and migration of HCC at least partly through targeting BIRC3 and regulating NF-κB signaling pathway, and it may be a therapeutic target for HCC prognosis.

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