MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down-regulating the expression of MCL-1
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Qing Xie1,*, Shuai Wang2,*, Yue Zhao1, Zhenchao Zhang2, Chuan Qin1, Xianjun Yang1
1Tumor Signaling and Transduction Lab, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang City, Henan Province, 453003, PR China
2Department of Human Parasitology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang City, Henan Province, 453003, PR China
*These authors have contributed equally to this work
Qing Xie, email: [email protected]
Keywords: BCSCs, miR-519d, cisplatin, resistance, MCL-1
Received: December 28, 2016 Accepted: January 25, 2017 Published: February 28, 2017
Cancer stem cells are considered as the cell population which is responsible for chemoresistance and treatment failure in breast cancer patients. Therefore, it is urgent to explore the mechanism by which cancer stem cells survive under the treatment of chemotherapeutic drugs such as cisplatin. In this paper, we demonstrated significant decrease of miR-519d in breast cancer stem cells by quantitative RT-PCR analysis. Furthermore, we found the enforced expression of miR-519d in T-47D-cancer stem cells significantly increased their sensitivity to cisplatin through the apoptosis pathway. In addition, the gene of MCL-1, which is a member of pro-apoptotic Bcl-2 family, was found to be the target of miR-519d in T-47D-cancer stem cells. Our date demonstrated that enforced miR-519d expression enhanced the cisplatin-induced apoptosis through the MCL-1 dependent mitochondria pathway in breast cancer stem cells. Taken together, the present study suggests that miR-519d reduces chemoresistance in breast cancer stem cells, and understanding of miR-519d may be helpful for increasing the efficacy of chemotherapy.
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