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

作者：Xiangxiang Liu, Weiguang Zheng, Lian Zhang, Ziyi Cao, Xianling Cong, Qianying Hu, Jingyao Hou, Xin Jin, Qingxia Yuan, Luyao Lin, Jiang Tan, Jun Lü, Yu Zhang, Na Zhang · 发表于：Cancer Letters · 年份：2024 · DOI：10.1016/j.canlet.2024.216707 · 被引用次数：9 · 研究领域：Cancer-related gene regulation、Epigenetics and DNA Methylation、RNA modifications and cancer

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.