IGF2BP3以m6A依赖方式增强GSDMD稳定性并阻断JNK信号促进眼睑基底细胞癌焦亡

Abstract

Purpose This study aimed to uncover the mechanism of IGF2BP3/GSDMD axis by modulating JNK signaling activation in eyelid basal cell carcinoma (BCC).Methods Human BCC cell line (TE354.T) was transfected vectors targeting IGF2BP3 and GSDMD. Following transfection, changes in cell proliferation, migration, invasion, pyroptosis, and inflammatory response were monitored. Protein expression analysis was done with specific antibodies (IGF2BP3, GSDMD, GSMDM-N, p20, IL-1β, IL-18, JNK, p-JNK, and p-c-JUN). IGF2BP3 and GSDMD co-localization in TE354.T cells were observed. The m6A modification of GSDMD mRNA was detected by gene-specific m6A qPCR assay. Tumor growth was observed in nude mice.Results By stabilizing GSDMD mRNA, IGF2BP3 reduced eyelid BCC proliferation, invasion, and migration, and increased pyroptosis. IGF2BP3 regulated the expression and translational output of GSDMD in TE354.T cells. IGF2BP3/GSDMD axis acted in BCC by blocking JNK pathway activation. IGF2BP3 inhibited tumor formation by promoting GSDMD stability.Conclusions IGF2BP3 enhances GSDMD stability and blocks JNK signaling activation to promote eyelid BCC pyroptosis in an m6A-Dependent Manner.