Arginine methylation-dependent cGAS stability promotes non-small cell lung cancer cell proliferation

• Published in: Cancer letters 2024-04, Vol.586, p.216707-216707, Article 216707
• Main Authors: Liu, Xiangxiang, Zheng, Weiguang, Zhang, Lian, Cao, Ziyi, Cong, Xianling, Hu, Qianying, Hou, Jingyao, Jin, Xin, Yuan, Qingxia, Lin, Luyao, Tan, Jiang, Lu, Jun, Zhang, Yu, Zhang, Na
• Format: Article
• Language: English
• Subjects: AKT pathway; Arginine methylation; cGAS; NSCLC; PRMT1
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2024.216707

Cyclic GMP-AMP synthase (cGAS), promotes non-small cell lung cancer (NSCLC) cell proliferation. However, the specific mechanisms of cGAS-mediated NSCLC cell proliferation are largely unknown. In this study, we found asymmetric dimethylation by protein arginine methyltransferase 1 (PRMT1) at R127 of cGAS. This facilitated the binding of deubiquitinase USP7 and contributed to deubiquitination and stabilization of cGAS. PRMT1-and USP7-dependent cGAS stability, which also played a pivotal role in accelerating NSCLC cell proliferation through activating AKT pathway. We validated that the expression of cGAS and PRMT1 were positive correlated in human non-small cell lung cancer samples. Our study demonstrates a unique mechanism for managing cGAS stability by arginine methylation and indicates that PRMT1-cGAS-USP7 axis is a potential therapeutic target for NSCLC. •Methylation of cGAS R127 by PRMT1 recruits USP7, which results in the deubiquitination and stabilisation of cGAS.•cGAS R127 methylation promotes NSCLC cell proliferation.•Methylated cGAS R127 binds to the PDK1 and AKT, activating AKT pathway.•The expression of cGAS and PRMT1 were positive correlated in NSCLC samples.