Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea.
Natural Products Research Institute, KIST Gangneung, Gangneung 25451, Korea.
Int J Mol Sci. 2022 Oct 14;23(20):12323. doi: 10.3390/ijms232012323.
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 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.
蛋白质精氨酸甲基转移酶 7（PRMT7）调节多种细胞反应，包括基因表达、细胞迁移、应激反应和干细胞特性。在这项研究中，我们通过 SGC8158 处理或其特异性 siRNA 转染抑制 PRMT7 活性，研究了 PRMT7 在细胞周期进程和 DNA 损伤反应（DDR）中的生物学作用。抑制 PRMT7 导致细胞周期在 G 期停滞，这是由于 p21 蛋白的稳定和随后的积累。此外，PRMT7 活性与 DNA 修复途径密切相关，包括同源重组和非同源末端连接。有趣的是，SGC8158 与阿霉素联合使用，导致 MCF7 细胞中的 DNA 损伤和细胞毒性协同增加。总之，我们的数据表明 PRMT7 是细胞生长和 DDR 的关键调节剂，表明它是癌症治疗的一个有前途的靶点。
