PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity
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초록

Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 in cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at the G(1) phase, resulting from the stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, including both homologous recombination and non-homologous end-joining. Interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxicity in MCF7 cells. Taken together, our data demonstrate that PRMT7 is a critical modulator of cell growth and DDR, indicating that it is a promising target for cancer treatment.

키워드

protein arginine methyltransferase 7SGC8158DNA damage responsesenescencecell cycleMETHYLTRANSFERASE 7 PRMT7ARGININE METHYLATIONPHOSPHORYLATIONMECHANISMCANCERREPAIRBRCA253BP1
제목
PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity
저자
Jeong, AhyeonCho, YenaCho, MinkyeongBae, Gyu-UnSong, Dae-GeunKim, Su-NamKim, Yong Kee
DOI
10.3390/ijms232012323
발행일
2022-10
유형
Article
저널명
International Journal of Molecular Sciences
23
20