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PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer.

PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer.
Author Information (click to view)

Wang Z, Kong J, Wu Y, Zhang J, Wang T, Li N, Fan J, Wang H, Zhang J, Ling R,


Wang Z, Kong J, Wu Y, Zhang J, Wang T, Li N, Fan J, Wang H, Zhang J, Ling R, (click to view)

Wang Z, Kong J, Wu Y, Zhang J, Wang T, Li N, Fan J, Wang H, Zhang J, Ling R,

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Breast cancer research and treatment 2017 11 28() doi 10.1007/s10549-017-4597-6

Abstract
PURPOSE
Acquired resistance to chemotherapeutic agents in breast cancer is a major clinical challenge. Recent studies have shown that the emergence of cancer stem cells contributes to the development of drug resistance, and the protein arginine methyltransferase 5 (PRMT5) was crucial for the maintenance of stemness. However, the roles of PRMT5 in breast cancer cell stemness and the development of cancer drug resistance have not been clarified. In this study, we investigated the effect of PRMT5 on the sensitivity to doxorubicin and cell stemness in breast cancer.

METHODS
PRMT5 expression was assessed in a panel of breast cancer cell lines (MDA-MB-231, MCF7, T-47D, BT-474, Au-565) and normal mammal epithelial cells (MCF10A). For knockdown of PRMT5 expression, two pairs of shRNAs as well as a control shRNA were utilized. Meanwhile, the wild-type PRMT5 and its catalytically dead counterpart (R368A) were stably overexpressed in MDA-MB-231 and MCF7 cells. The sensitivity to doxorubicin was determined by MTT assays, TUNEL assays, and Western blot analyses. To evaluate the degree of cell stemness, CD24/CD44-sorting and mammosphere formation experiments were performed.

RESULTS
We demonstrated that PRMT5 regulates OCT4/A, KLF4, and C-MYC in breast cancer to govern stemness and affects the doxorubicin resistance of breast cancer.

CONCLUSION
Our study suggests that PRMT5 may play an important role in the doxorubicin resistance of breast cancer.

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