The m6A methyltransferase RBM15 promotes gastric cancer progression by stabilizing KLF5 expression to suppress the p53 signaling pathway.

N6-adenosine methylation (m6A), a prevalent post-transcriptional regulatory mechanism in eukaryotes, plays a pivotal role in tumorigenesis. Our study demonstrates that RBM15 is significantly upregulated in gastric cancer (GC) and correlates with poor prognosis. Functionally, RBM15 promotes malignant phenotypes including proliferation, migration, invasion, and anti-apoptosis in GC cells. Mechanistically, RBM15 binds and stabilizes KLF5 mRNA through IGF2BP2-dependent m6A modification, thereby suppressing the p53 signaling pathway and its downstream effectors p21/PUMA. In vivo research revealed that RBM15 drives tumorigenesis through the KLF5/p53 axis. Notably, precise targeting of RBM15 in PDX models effectively curbs tumor growth. These findings first establish the oncogenic role of the RBM15-KLF5-p53 regulatory axis in GC, providing novel insights for prognostic evaluation and targeted therapy.