IGF2BP1‐Mediated m6A Modification Enhances the Stability of circ_0088302 to Promote Gastric Cancer Progression

Abstract

Background: Circular RNAs (circRNAs) are recognized as critical regulators of gastric cancer (GC) progression. Nevertheless, the biological function of circ_0088302 in gastric cancer and its epitranscriptomic regulatory mechanism remain unclear. Methods: The expression of circ_0088302 was analyzed based on plasma circRNA data from GSE93541 and RT‐qPCR, and its subcellular localization was determined by RNA‐FISH. Cellular malignant phenotypes were evaluated using CCK‐8 assay, colony‐formation assay, wound‐healing assay, Transwell assay, and flow cytometry. MeRIP‐qPCR, RIP, dual‐luciferase reporter assay, and actinomycin D assay were performed to assess m6A modification, IGF2BP1 binding, candidate m6A sites, and RNA stability. AVJ16 was used to inhibit IGF2BP1 function. Results: circ_0088302 was highly expressed in plasma samples from GC patients and GC cells. Knockdown of circ_0088302 repressed cell viability, colony formation, and migration, and promoted cell apoptosis. circ_0088302 exhibited m6A enrichment and bound to IGF2BP1, and the predicted 292 site was involved in IGF2BP1‐dependent regulation. IGF2BP1 knockdown reduced circ_0088302 levels and accelerated its degradation. AVJ16 suppressed the viability of GC cells and abrogated the malignant phenotypes induced by circ_0088302 overexpression. Conclusion: IGF2BP1 may facilitate the malignant phenotypes of GC cells by maintaining the RNA stability of m6A‐modified circ_0088302, suggesting that the IGF2BP1/circ_0088302 axis may represent a potential therapeutic target for GC.