Cell-free microRNA-21: biomarker for intracranial aneurysm rupture

BACKGROUND: Deregulation of miRNA-21 expression has been reported to be associated with vascular smooth muscle behavior and cytoskeletal stability. This study is aimed to investigate the density of serum miRNA-21 in patients with different phases of intracranial aneurysms (IAs) and explore its warning function for IA rupture. METHODS: A total of 16 in 200 IA patients were selected and categorized into 4 groups based on the phase of IA. Microarray study was carried out using serum miRNA and differentially expressed miRNAs were identified. Another 24 samples from a cohort of 360 patients were added and real-time polymerase chain reaction (RT-PCR) was performed on expanded sample size (n = 40) for miRNA-21 validation. Potential gene targets of miRNA-21 were screened out from Gene Ontology (GO) database and literatures. RESULTS: Microarray study identified 77 miRNAs with significantly different expression levels between experimental groups and the control group. RT-PCR assays validated significant downregulation of miRNA-21 in experimental groups, among which miRNA-21 expression level of daughter aneurysm group decreased the most. Bioinformatic analyses revealed that several target genes related with miRNA-21 may be involved in IA formation and rupture. CONCLUSIONS: This study suggested that miRNA-21 had a protective effect for intracranial vascular wall against remodeling and warning function for intracranial aneurysm rupture. Significant suppression of serum miRNA-21 in IA patients may provide diagnostic clues for aneurysm rupture and guide clinical intervention.