Research Paper Volume 11, Issue 9 pp 2551—2564
MiR-124 sensitizes cisplatin-induced cytotoxicity against CD133+ hepatocellular carcinoma cells by targeting SIRT1/ROS/JNK pathway
- 1 Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 2 Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 3 Department of Hepato-Billiary Surgery, Dongguan people’s Hospital, Southern Medical University, Guangdong 523905, China
- 4 Department of Thyroid Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 5 Department of Blood Transfusion, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
- 6 Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 7 Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Received: January 27, 2018 Accepted: April 6, 2019 Published: May 5, 2019
https://doi.org/10.18632/aging.101876How to Cite
Copyright: Xu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.