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Article

PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer

1
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3
Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
4
Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Amabile Maria Ida
J. Pers. Med. 2021, 11(10), 1009; https://doi.org/10.3390/jpm11101009
Received: 30 August 2021 / Revised: 28 September 2021 / Accepted: 29 September 2021 / Published: 8 October 2021
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
Treatment of triple-negative breast cancer (TNBC) remains an unmet clinical need owing to its lack of an efficient therapeutic target. The targeting of DNA repair by poly(ADP-ribose) polymerase (PARP) inhibitors has shown benefit for patients with the BRCA variation. However, sensitivities to the PARP inhibitors were reported regardless of BRCA status. Thus, exploring the underlying mechanisms is imperative. Herein, we identified that breast cancer cells with an elevated expression of protein arginine methyl transferase 1 (PRMT1) was associated with therapeutic sensitivity to the PARP inhibitor olaparib. The results of cell viability and colony formation assays indicated that the suppression of PRMT1 by small hairpin RNA or by the chemical inhibitor increased sensitivity to olaparib in human TNBC MDA-MB-231 and BT549 cells. Bioinformatic analysis revealed that PRMT1 expression was significantly associated with the MYC signature, and TNBC cells with higher PRMT1 and the MYC signature were associated with therapeutic sensitivity to olaparib. Mechanistic studies further demonstrated that knockdown of PRMT1 reduced the c-Myc protein level and downregulated the expression of MYC downstream targets, whereas overexpression of PRMT1 enhanced c-Myc protein expression. Moreover, the overexpression of PRMT1 promoted c-Myc protein stability, and the inhibition of PRMT1 downregulated c-Myc protein stability. Accordingly, the knockdown of PRMT1 inhibited homologous recombination gene expression. These data indicate that PRMT1 is instrumental in regulating DNA repair, at least in part, by modulating c-Myc signaling. Our data highlighted the PRMT1/c-Myc network as a potential therapeutic target in patients with TNBC. View Full-Text
Keywords: c-Myc; PRMT1; olaparib; triple-negative breast cancer c-Myc; PRMT1; olaparib; triple-negative breast cancer
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MDPI and ACS Style

Hsu, W.-J.; Chen, C.-H.; Chang, Y.-C.; Cheng, C.-H.; TsaI, Y.-H.; Lin, C.-W. PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer. J. Pers. Med. 2021, 11, 1009. https://doi.org/10.3390/jpm11101009

AMA Style

Hsu W-J, Chen C-H, Chang Y-C, Cheng C-H, TsaI Y-H, Lin C-W. PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer. Journal of Personalized Medicine. 2021; 11(10):1009. https://doi.org/10.3390/jpm11101009

Chicago/Turabian Style

Hsu, Wen-Jing, Cheng-Hsun Chen, Yu-Chu Chang, Chia-Hsiung Cheng, Ying-Huei TsaI, and Cheng-Wei Lin. 2021. "PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer" Journal of Personalized Medicine 11, no. 10: 1009. https://doi.org/10.3390/jpm11101009

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