IGF2BP3 promotes progression of head and neck cancers through the circHECTD2/hsa_miR_4310/7157-5p/Smad2 signaling axis in an m6A modification–dependent manner

Accumulating evidence indicates that N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) plays a pivotal role in regulating cancer progression. However, in head and neck squamous cell carcinoma (HNSCC), the biological functions and underlying mechanisms of m6A modification in circRNAs remain insufficiently elucidated. In this study, we demonstrated that IGF2BP3, an upstream m6A reader, is associated with poor clinical outcomes. IGF2BP3 stabilizes circHECTD2 through binding, and m6A modification enhances this interaction. Mechanistic investigations revealed that IGF2BP3 binds to and stabilizes circHECTD2, which functions as a sponge for hsa-miR-4310 and hsa-miR-7157-5p, thereby preventing the degradation of SMAD2 mRNA and promoting tumor proliferation, invasion, and metastasis in HNSCC. Collectively, these findings suggest that IGF2BP3 and circHECTD2 may serve as promising prognostic biomarkers and therapeutic targets for HNSCC.