Li Chao, Miao Runchen, Liu Sushun, Wan Yong, Zhang Simin, Deng Yan, Bi Jianbin, Qu Kai, Zhang Jingyao, Liu Chang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Oncotarget. 2017 Apr 25;8(17):28683-28695. doi: 10.18632/oncotarget.15640.
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.
微小RNA在肝癌的发生和发展中起重要作用。在本研究中,我们发现miR-146b-5p的下调与肝细胞癌(HCC)患者的肿瘤生长、转移及不良预后相关。miR-146b-5p在体外和体内均可抑制细胞增殖、迁移和侵袭并诱导细胞凋亡。值得注意的是,肿瘤坏死因子受体相关因子6(TRAF6)被证实为HCC中miR-146b-5p的直接靶点,且miR-146b-5p通过抑制TRAF6介导的Akt磷酸化发挥肿瘤抑制作用。此外,我们鉴定出长链非编码RNA MALAT1作为miR-146b-5p的分子海绵,可下调其在HCC中的表达。总体而言,我们的结果表明miR-146b-5p通过靶向TRAF6介导的Akt磷酸化抑制HCC的肿瘤生长和转移。