The mechanism of RGS5 regulating gastric cancer mismatch repair protein

Abstract The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4‐gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low‐risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c‐Myc. Furthermore, co‐immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c‐Myc. Additionally, we confirmed that RGS5 regulates c‐Myc through the ubiquitin‐proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD‐L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.