Journal
AGING-US
Volume 11, Issue 9, Pages 2551-2564Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101876
Keywords
miR-124; SIRT1; ROS; JNK; cisplatin; HCC
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Funding
- Provincial basic and applied basic research project (provincial natural fund) Doctor startup project [2016A030310089]
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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.
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