MiR-124 sensitizes cisplatin-induced cytotoxicity against CD133 hepatocellular carcinoma cells by targeting SIRT1/ROS/JNK pathway.

Drug resistance is still a major obstacle for efficient treatment of hepatocellular carcinoma (HCC) during the cisplatin-based chemotherapy. Recent studies have demonstrated that CD133 positive population of cancer cells are responsible for multiple drug resistance. We are supposed to take strategies to sensitize CD133 HCC cells to cisplatin treatment. In the present study, CD133 HCC cells showed significant cisplatin-resistance compared to the CD133 HCC cells. Downregulation of miR-124 was observed in CD133 HCC cells. However, enforced expression of miR-124 can increase the sensitivity of CD133 HCC cells to cisplatin treatment in vitro and in vivo. Mechanically, overexpression of miR-124 was found to inhibit the expression of SIRT1 and thus promoted the generation of ROS and phosphorylation of JNK. As the results, overexpression of miR-124 expanded the apoptosis in cisplatin-treated CD133 HCC cells. We then demonstrated that overexpression of miR-124 sensitized cisplatin-induced cytotoxicity against CD133 hepatocellular carcinoma cells by targeting SIRT1/ROS/JNK pathway.