Zu Yong, Yang Yanhong, Zhu Jiyun, Bo Xiaobo, Hou Shuangxing, Zhang Bo, Qiu Jiangfeng, Zheng Jing
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology 130 Meilong Road, Shanghai, China.
Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University, School of Medicine 160 Pujian Road, Shanghai, China.
Am J Cancer Res. 2016 Nov 1;6(11):2502-2513. eCollection 2016.
MicroRNAs have been proven to play important roles in many biological processes such as cellular growth and differentiation, apoptosis, and modulation of host response to viral infection. In the present study, we find that the expression of miR-146a was decreased in hepatocellular carcinoma (HCC) tissues compared with corresponding adjacent tissues, and the expression level in HCC cell lines was lower than in a normal liver cell. Over-expression suppressed the proliferation and invasion of HCC cells. In addition, luciferase reporter assays and western blotting confirmed that miR-146a directly target TRAF6 which attenuated the effect of miR-146a on cell proliferation and invasion in HepG2 and SMMC7721 cells. Meanwhile, lentivirus-mediated increased expression of miR146a repressed tumor formation in nude mice. Taken together, our findings demonstrate that miR-146a suppresses HCC by down-regulating TRAF6. We also discovered that miR-146a may represent a novel potential candidate of the HCC carcinoma diagnostic marker in the long term.
微小RNA已被证明在许多生物学过程中发挥重要作用,如细胞生长和分化、细胞凋亡以及宿主对病毒感染反应的调节。在本研究中,我们发现与相应的癌旁组织相比,miR-146a在肝细胞癌(HCC)组织中的表达降低,且在肝癌细胞系中的表达水平低于正常肝细胞。过表达抑制了肝癌细胞的增殖和侵袭。此外,荧光素酶报告基因检测和蛋白质印迹证实miR-146a直接靶向TRAF6,这减弱了miR-146a对HepG2和SMMC7721细胞增殖和侵袭的影响。同时,慢病毒介导的miR146a表达增加抑制了裸鼠体内肿瘤的形成。综上所述,我们的研究结果表明miR-146a通过下调TRAF6抑制肝癌。我们还发现,从长远来看,miR-146a可能代表一种新型的潜在肝癌诊断标志物候选物。