M7G Methylation-Regulated Genes Coordinate Gastric Cancer Proliferation and Immune Evasion: Functional Characterization of WDR4 and BUD23

The N7-methylguanosine (m7G) epitranscriptome represents a pivotal regulatory layer in cancer biology, yet its integrative control of malignant progression remains elusive. In this study, we identified candidate master regulator (MR) proteins and synthesized a m7G master regulatory network describing the interactions linking m7G genomic events to MRs representing the key effectors of the m7G mutational landscape. Through transcriptomics and proteomics, we revealed the connection between m7G genomic landscapes and tumor microenvironment reprogramming and uncover a coordinated tumor suppression paradigm mediated by m7G writer WDR4 and BUD23 in gastric cancer. Functional interrogation demonstrated that WDR4/BUD23 co-regulation restricts tumor cell proliferation and suppresses epithelial-mesenchymal transition (EMT). Furthermore, functional validation has established WDR4 and BUD23 as key orchestrators of tumor-immune coevolution, where their synergistic activity reshapes immunosuppressive microenvironments while simultaneously engaging checkpoint signaling nodes. We present the first comprehensive characterization of WDR4 and BUD23 as m7G writers in gastric cancer, identifying their tumor-suppressive roles and therapeutic potential. Our findings proposed a novel therapeutic strategy combining m7G-targeted intervention and immunomodulation for gastric cancer management.