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

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.

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.

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.

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.

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.