Abstract
Primary multiple intracranial aneurysm (MIA) is a vascular disease that frequently leads to fatal vascular rupture and subarachnoid hemorrhage. However, the epigenetic regulation associated with MIA has remained largely elusive. Circular RNAs (circRNAs) serve important roles in cardiovascular diseases; however, their association with MIA has remained to be investigated. The present study initially aimed to explore novel mechanisms of MIA through examining circRNA expression profiles. Comprehensive circRNA expression profiles were detected by RNA sequencing (RNA-Seq) in human peripheral blood mononuclear cells. The RNA-Seq results were validated by reverse transcription-quantitative PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested the functions of these circRNAs. A competing endogenous RNA network was constructed to reveal the circRNA-microRNA-mRNA relationship. Among the 3,328 differentially expressed circRNAs between the MIA and matched control groups, 60 exhibited significant expression changes (|log2 fold change|≥2; P<0.05). Among these 60 circRNAs, 20 were upregulated, while the other 40 were downregulated. A number of downregulated circRNAs were involved in inflammation. The most significant KEGG pathway was 'leukocyte transendothelial migration'. The circRNAs Homo sapiens (hsa)_circ_0135895, hsa_circ_0000682 and hsa_circ_0000690, which were also associated with the above-mentioned pathway, were indicated to be able to regulate protein tyrosine kinase 2, protein kinase Cβ and integrin subunit αL, respectively. To the best of our knowledge, the present study was the first to perform a circRNA sequencing analysis of MIA. The results specifically predicted the regulatory role of circRNAs in the pathogenesis of MIA. 'Leukocyte transendothelial migration' may be critical for the pathogenesis of MIA.