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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.

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