circ_0103896/miR-432-5p/FTO feedback loop suppresses the formation and progression of intracranial aneurysm.

Circular RNAs (circRNAs) and m(6)A RNA methylation play crucial roles in the pathogenesis of intracranial aneurysm (IA); however, their regulatory interplay remains unclear. Through circRNA profiling of 16 IA tissues and 8 superficial temporal arteries, we identified hsa_circ_0103896 as significantly downregulated in IA. RT-qPCR analysis further revealed that decreased circ_0103896 or increased miR-432-5p expression correlated with IA progression. Functional assays demonstrated that circ_0103896 inhibited the phenotypic switch of human brain vascular smooth muscle cells (hBVSMCs) from a contractile to a synthetic state, whereas circ_0103896 knockdown reversed this effect. In vivo, circ_0103896 overexpression alleviated IA severity, whereas its depletion aggravated aneurysm formation. Mechanistically, circ_0103896 functioned as a sponge for miR-432-5p, thereby upregulating FTO, which in turn promoted m(6)A demethylation of circ_0103896. This process reinforced circ_0103896 expression, forming a positive feedback loop. The circ_0103896/miR-432-5p/FTO axis thus suppresses hBVSMC phenotypic transformation and mitigates IA progression. These findings reveal a novel epigenetic mechanism involving m(6)A modification and circRNA-miRNA crosstalk in IA pathogenesis, highlighting circ_0103896 as a potential therapeutic target.