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

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 activi...

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Published in:International journal of molecular sciences 2022-10, Vol.23 (20), p.12323
Main Authors: Jeong, Ahyeon, Cho, Yena, Cho, Minkyeong, Bae, Gyu-Un, Song, Dae-Geun, Kim, Su-Nam, Kim, Yong Kee
Format: Article
Language:English
Subjects:
Cancer
Cell cycle
Cellular stress response
Cyclin-dependent kinases
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA damage
DNA damage response
DNA methylation
DNA repair
Doxorubicin
G1 phase
Gene expression
Genomes
GTP-binding protein
Homologous recombination
Homology
Kinases
Non-homologous end joining
Phosphorylation
Protein arginine methyltransferase
protein arginine methyltransferase 7
Proteins
Senescence
SGC8158
siRNA
Transfection
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Summary: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 G1 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232012323