Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82
Weiqi Dai1, Chengfen Wang1, Fan Wang1
1Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
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.
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