Prognostic value of miR-423-5p in intracranial aneurysm and its mechanism in regulating human brain vascular smooth muscle cell function via SMAD3

BACKGROUND: Intracranial aneurysm (IA) is a life-threatening cerebrovascular disorder. MicroRNAs exert crucial regulatory functions in IA. However, the role and mechanism of miR-423-5p in IA remain unclear. AIM: To clarify the association between miR-423-5p and the prognosis of IA, and to explore its regulatory effect and mechanism on human brain vascular smooth muscle cells (HBVSMCs). METHODS: 122 IA patients and 90 healthy controls were included. Serum levels of miR-423-5p, SMAD3, and phenotypic markers were measured using RT-qPCR. MTT and Transwell assays were used to assess cell proliferation and migration. A dual-luciferase reporter gene assay, along with bioinformatics analysis, served to confirm the targeting relationship between miR-423-5p and SMAD3. Furthermore, co-transfection was performed to investigate its functions in IA molecular mechanisms. RESULTS: In IA patients, serum miR-423-5p expression was notably increased. The miR-423-5p expression was significantly associated with aneurysm rupture (p = 0.002) and independently predicted poor outcomes in IA patients. In HBVSMCs, miR-423-5p significantly promoted cell proliferation, migration, phenotypic transformation, and inflammation (inhibited α-SMA/calponin, promoted IL-1β/MMP-9), while the inhibitor exerted the opposite effects. MiR-423-5p directly targeted SMAD3 and suppressed its expression. Overexpressing SMAD3 reversed miR-423-5p-induced pro-pathological effects on HBVSMCs. CONCLUSIONS: In IA patients, miR-423-5p is significantly overexpressed and acts as an independent prognostic indicator for unfavorable outcomes. By targeting and inhibiting SMAD3, it facilitates the phenotypic transformation of HBVSMCs, thereby contributing to the progression of IA.