Differentially expressed circular RNA profile in hemorrhagic and ischemic moyamoya disease

Hemorrhage is a frequent manifestation in patients with moyamoya disease (MMD). Compared with MMD patients with other subtypes, patients with hemorrhagic MMD (hMMD) are at higher risk of poor prognostic outcomes, Circular RNAs (circRNAs) frequently display dysregulated expression in several human diseases. In the present study, the role of circRNAs in the pathogenesis of hemorrhage in MMD was investigated. Microarray profiling on 12 moyamoya disease samples, consisting of six hMMD and six matching ischemic MMD (iMMD) samples, was performed. Reverse transcription-quantitative PCR was then used to confirm the microarray analysis findings. Bioinformatics tools, including Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were used for further assessment. A network map of circRNA-microRNA-gene interactions was also constructed. In total, 3,607 differentially expressed circRNAs, in which 1,940 circRNAs were upregulated and 1,967 circRNAs were downregulated, were identified in hMMD (fold change ≥2.0 and P<0.05) samples. Gene Ontology revealed that the differentially expressed circRNAs were mainly involved in 'cell cycle phase transition' and 'mitotic cell cycle phase transition'. In addition, the ubiquitin mediated proteolysis pathway was found to be the most significantly enriched pathway in hMMD samples. The results of the present study suggested that clusters of circRNAs were differently expressed in hMMD compared with those in iMMD samples, which provides novel insights into hemorrhage in moyamoya disease pathophysiology and potential targets for future therapy.