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

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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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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos. 81572917 and 81372390).

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Author notes

  1. Zhe Wang and Jing Kong contributed equally to this study.

Authors and Affiliations

  1. Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Zhe Wang, Jing Kong, Ying Wu, Juliang Zhang, Ting Wang, Nanlin Li, Jing Fan, Hui Wang & Rui Ling

  2. The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Jian Zhang

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  1. Zhe Wang
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Correspondence to Jian Zhang or Rui Ling.

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Wang, Z., Kong, J., Wu, Y. et al. PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer. Breast Cancer Res Treat 168, 531–542 (2018). https://doi.org/10.1007/s10549-017-4597-6

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  • DOI: https://doi.org/10.1007/s10549-017-4597-6

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