Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82

作者:Dai, Weiqi; Wang, Chengfen; Wang, Fan; Wang, Yugang; Shen, Miao; Chen, Kan; Cheng, Ping; Zhang, Yan; Yang, Jing; Zhu, Rong; Zhang, Huawei; Li, Jingjing; Zheng, Yuanyuan; Lu, Jie; Zhou, Yingqun; Xu, Ling*; Guo, Chuanyong
来源:Biochemical and Biophysical Research Communications, 2014, 446(2): 541-548.
DOI:10.1016/j.bbrc.2014.03.006

摘要

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.