Circ_0008433 Facilitates Phenotypic Transition of Vascular Smooth Muscle Cells via HuR in Intracranial Aneurysm.

OBJECTIVE: Intracranial Aneurysm (IA) is characterized by vascular wall degeneration driven by Vascular Smooth Muscle Cell (VSMC) phenotypic switching. Circular RNAs (circRNAs) are emerging regulators of vascular biology; however, the role of circ_0008433 in IA remains unclear. This study investigated whether circ_0008433 regulates VSMC phenotypic switching through the RNA-binding protein HuR. METHODS: circ_0008433 and HuR expression were assessed in IA tissues and control arteries. Human brain VSMCs were transfected with circ_0008433 overexpression or knockdown constructs, with or without HuR silencing. RNA immunoprecipitation (RIP) assays were used to evaluate the interaction between circ_0008433 and HuR. Cell proliferation, migration, and phenotypic markers were assessed using the CCK-8 assay, Transwell assay, qRT-PCR, and Western blotting. RESULTS: circ_0008433 and HuR were significantly upregulated in IA tissues and VSMCs. RIP assays confirmed an interaction between circ_0008433 and HuR. circ_0008433 overexpression was associated with increased HuR mRNA and protein expression and promoted VSMC proliferation, migration, and synthetic phenotype switching, as indicated by increased MMP2 and MMP9 and decreased α-SMA and SM22α expression. These effects were abolished by HuR knockdown. DISCUSSION: These findings identify the circ_0008433-HuR axis as a novel regulatory pathway in IA-associated vascular remodeling. The study suggests that circ_0008433 may contribute to aneurysm pathogenesis by promoting VSMC phenotypic switching via HuR-dependent mechanisms, highlighting its potential as a candidate biomarker and therapeutic target for intracranial aneurysm. Further investigation into the precise molecular mechanisms and clinical translation of this axis is warranted. CONCLUSION: circ_0008433 promotes VSMC phenotypic switching and may contribute to IA progression through a HuR-dependent mechanism. These findings provide insight into the molecular mechanisms underlying IA-associated vascular remodeling and identify the circ_0008433-HuR axis as a potential target for further investigation.