MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down-regulating the expression of MCL-1

Abstract

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.