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Breast Cancer Research and Treatment

, Volume 168, Issue 2, pp 531–542 | Cite as

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

  • Zhe Wang
  • Jing Kong
  • Ying Wu
  • Juliang Zhang
  • Ting Wang
  • Nanlin Li
  • Jing Fan
  • Hui Wang
  • Jian ZhangEmail author
  • Rui LingEmail author
Brief Report
  • 636 Downloads

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.

Keywords

Breast cancer PRMT5 Cancer stem cell Doxorubicin resistance 

Notes

Acknowledgments

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Thyroid, Breast and Vascular SurgeryXijing Hospital, The Fourth Military Medical UniversityXi’anChina
  2. 2.The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular BiologyThe Fourth Military Medical UniversityXi’anChina

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