RBM15 aggravates endometrial cancer progression by inducing PBK m6A modification to inhibit the p53 pathway.

Endometrial cancer (EC) is one of the most pervasive gynecological malignancies, with its incidence increasing annually. Although progress has been made, the underlying molecular mechanisms driving EC progression remain poorly understood. N-methyladenosine (mA) RNA modification is instrumental in tumor biology, but the function of the mA "writer" RNA-binding motif protein 15 (RBM15) in EC remains unclear. This study investigates the role of RBM15 through mA-dependent regulation of its downstream target. RBM15 expression was analyzed using the TNMplot database and validated by qRT-PCR in EC tissues and cell lines. Cell functional assays were conducted to assess the impact of RBM15 knockdown. Bioinformatics analytics and MeRIP-qPCR were used to identify mA-modified downstream targets of RBM15. Furthermore, RNA stability assay, correlation analysis, and Western blotting were employed to explore the underlying regulatory mechanisms. Rescue experiments were done to confirm functional interactions. RBM15 was significantly overexpressed in EC, and its silencing impeded EC cell proliferation, migration, and invasion. PBK was identified as a direct downstream target, with RBM15-mediated mA enrichment enhancing mRNA stability. PBK expression was positively correlated with RBM15 levels in patient samples. RBM15 silencing partially attenuated the PBK-driven promotive effects in EC cells. Mechanistically, RBM15 suppressed the p53 pathway by stabilizing PBK, resulting in decreased phospho-p53 protein levels. In summary, RBM15 promotes EC progression by enhancing mA-dependent stabilization of PBK mRNA, which in turn suppresses p53 signaling, revealing a novel RBM15-PBK-p53 axis as a potential treatment target.