Weiqi Dai1, Chengfen Wang1, Fan Wang1, Yugang Wang2, Miao Shen1, Kan Chen1, Ping Cheng1, Yan Zhang1, Jing Yang1, Rong Zhu1, Huawei Zhang1, Jingjing Li1, Yuanyuan Zheng1, Jie Lu1, Yingqun Zhou1, Ling Xu3, Chuanyong Guo4. 1. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. 2. Department of Gastroenterology, Tong Ren Hospital, Jiaotong University, School of Medicine, Shanghai, China. 3. Department of Gastroenterology, Tong Ren Hospital, Jiaotong University, School of Medicine, Shanghai, China. Electronic address: xuling606@sina.com. 4. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. Electronic address: guochuanyong@hotmail.com.
Abstract
AIM: To investigate the metastatic effects and mechanisms of miR-197 in hepatocellular carcinoma (HCC). METHODS AND RESULTS: The levels of miR-197 increased in HCC cells and tissues compared with a normal hepatic cell line (LO2) and adjacent nontumorous liver tissues, respectively. miR-197 expression negatively correlated with CD82 mRNA expression in these cell lines and tissues. Dual luciferase reporter assay and Western blot confirmed a direct interaction between miR-197 and CD82 3'UTR sequences. After miR-197 was silenced in HCC cells, CD82 expression increased. In the presence of human hepatocyte growth factor (HGF), cells silenced for anti-miR-197 exhibited elongated cellular tails and diminished lamellipodia due to reductions in both ROCK activity and the levels of Rac 1 protein. Downregulation of miR-197 along with the upregulation of CD82 in HCC cells resulted in the inhibition of HCC migration and invasion in vitro and in vivo. CONCLUSION: Taken together, these data suggest that anti-miR-197 suppresses HCC migration and invasion by targeting CD82. The regulation of the miR-197/CD82 axis could be a novel therapeutic target in future HCC effective therapy.
AIM: To investigate the metastatic effects and mechanisms of miR-197 in hepatocellular carcinoma (HCC). METHODS AND RESULTS: The levels of miR-197 increased in HCC cells and tissues compared with a normal hepatic cell line (LO2) and adjacent nontumorous liver tissues, respectively. miR-197 expression negatively correlated with CD82 mRNA expression in these cell lines and tissues. Dual luciferase reporter assay and Western blot confirmed a direct interaction between miR-197 and CD82 3'UTR sequences. After miR-197 was silenced in HCC cells, CD82 expression increased. In the presence of humanhepatocyte growth factor (HGF), cells silenced for anti-miR-197 exhibited elongated cellular tails and diminished lamellipodia due to reductions in both ROCK activity and the levels of Rac 1 protein. Downregulation of miR-197 along with the upregulation of CD82 in HCC cells resulted in the inhibition of HCC migration and invasion in vitro and in vivo. CONCLUSION: Taken together, these data suggest that anti-miR-197 suppresses HCC migration and invasion by targeting CD82. The regulation of the miR-197/CD82 axis could be a novel therapeutic target in future HCC effective therapy.