Introductions: There is increasing interest in identifying novel methods for intracranial aneurysm(IA) diagnosis. Non-coding RNA molecules such as microRNAs (miRNAs) are stable within the circulation and may serve as biomarkers for IA.
Hypothesis: This study aims to identify miRNAs associated with a diagnosis of human IA and to gain comprehensive insight into the molecular mechanism of formation and development of intracranial aneurysms (IAs) .
Methods: We included 45 patients with IAs and 35 normal controls. A microarray study was carried out using serum miRNAs. Differentially expressed miRNAs were identified. Then the differential expressed miRNAs screened out was validated in an independent cohort of 40 IAs patients and 30 controls using real-time quantitative reverse-transcription PCR (RT-PCR). And cluster analysis was performed in order to make the results looks more intuitive and potential gene targets were retrieved from miRNA target prediction databases.
Results: Microarray study identified 14 miRNAs which were significantly changed in the IAs patients at an adjusted significance level of P ≤ 0.05 and fold change ≥ 2. Among them 6 were up-regulated and 8 were down-regulated. Among the miRNAs identified, hsa-miR-23b-3p, miR-590-5p, miR-20b-5p and miR-142-3p were found to be significantly down-regulated between the IAs patients and control groups of the independent 70 individuals. A total of 3815 predicted target genes are related to the 14 differentially expressed miRNAs. Bioinformatic analysis revealed that several target genes were closely related to aneurysm formation, growth and rupture, such as TGM2, EDN1, AGT and EGER. Among them TGM2 played great roles in positive regulation of inflammatory response, smooth muscle cell proliferation and cell adhesion, at the same time participated in blood vessel remodeling.
Conclusions: Several serum miRNAs have been found to be associated with intracranial aneurysms, suggesting that miRNAs may participate in the regulation of the occurrence and development of intracranial aneurysms. All the 4 differently expressed miRNAs in aneurysm patients are down-regulated, which suggests reduced accumulation of special serum miRNAs may be a risk factor of the forming of intracranial aneurysms.