Role of ebv-circRPMS1–p53 interaction in the proliferation and clinical progression of Epstein–Barr virus-associated gastric carcinoma

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) represents a distinct clinicopathological entity with unique molecular characteristics, including latent EBV infection and dysregulation of host tumor suppressors. However, the functional interplay between EBV circular RNAs (ebv-circRNAs) and p53 protein remains enigmatic. This study explored the role of ebv-circRPMS1, a previously uncharacterized ebv-circRNA, in EBVaGC pathogenesis. To define ebv-circRPMS1-p53 interplay, siRNA knockdown (validated by RT-qPCR) modulated ebv-circRPMS1 in EBV+ cells. RIP/co-immunoprecipitation confirmed direct ebv-circRPMS1-p53 binding. EdU assays quantified proliferation. RNA-FISH/immunofluorescence mapped cytoplasmic colocalization. Xenografts evaluated in vivo tumorigenicity, while BaseScope/IHC analyzed tissues. Clinical cohort (n = 70) correlated co-expression with survival via Kaplan-Meier/Cox regression. This study demonstrated that ebv-circRPMS1 directly binds to p53, thereby enhancing tumor proliferation. Clinically, ebv-circRPMS1-p53 co-expression correlates with poor survival in EBVaGC patients. These findings unveil a novel viral strategy for subverting host tumor suppression, providing a rationale for targeting the ebv-circRPMS1-p53 axis in precision oncology.