Down-regulation of miR-146b-5p by long noncoding RNA MALAT1 in hepatocellular carcinoma promotes cancer growth and metastasis

// Chao Li 1 , Runchen Miao 1 , Sushun Liu 1 , Yong Wan 2 , Simin Zhang 1 , Yan Deng 1 , Jianbin Bi 1 , Kai Qu 1 , Jingyao Zhang 1 , Chang Liu 1 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China 2 Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Correspondence to: Chang Liu, email: liuchangdoctor@163.com Keywords: microRNA-146b-5p, hepatocellular carcinoma, TNF receptor associated factor 6, growth, metastasis Received: December 28, 2016 Accepted: January 25, 2017 Published: February 23, 2017 ABSTRACT MicroRNAs play an important role in liver cancer genesis and progression. In this study, we identified down-regulation of miR-146b-5p associated with tumor growth, metastasis and poor survival in hepatocellular carcinoma (HCC) patients. miR-146b-5p could suppress proliferation, migration, and invasion and induced apoptosis in vitro and in vivo . Remarkably, TNF receptor associated factor 6 (TRAF6) was confirmed as a direct target of miR-146b-5p in HCC and miR-146b-5p exerted the tumor suppression roles through inhibiting the phosphorylation of Akt mediated by TRAF6. Furthermore, we identified long non-coding RNA MALAT1 as a molecular sponge of miR-146b-5p to down-regulate its expression in HCC. In general, our results indicate that miR-146b-5p inhibits tumor growth and metastasis of HCC by targeting TRAF6 mediated Akt phosphorylation.