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

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.