Circular RNA profiling of neutrophil transcriptome provides insights into asymptomatic Moyamoya disease

Moyamoya disease (MMD) is a rare cerebrovascular disorder with higher incidences in Eastern Asian countries but the natural course remains uncertain. Circular RNAs (circRNAs) have been implicated in brain disorders, but their role in the development of MMD is unclear. Neutrophil depletion has been shown to affect stem cell migration, fate, and therapeutic outcomes. We investigated the circRNAs expression profile of neutrophil transcriptome in patients with asymptomatic MMD. Microarray based circRNAs profiling was determined between neutrophil samples from patients with asymptomatic MMD and healthy subjects. The microarray results were followingly confirmed by quantitative reverse-transcription PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses (KEGG) were adopted for annotation and predicting the functions of differentially expressed circRNAs. From this comparative circRNA microarray analysis of neutrophil samples from patients with asymptomatic MMD and healthy subjects, 123 circRNAs were identified differentially expressed between the two groups. Of these, 54 were upregulated and 69 were downregulated compared to controls (fold change >2.0 and P < 0.05). GO and KEGG analyses revealed that the differentially expressed circRNAs were mainly involved in immune responses, angiogenesis and metabolism in asymptomatic MMD. Besides, the hypoxia inducing factor-1α signaling pathway was found to be the critical pathway involved in the angiogenesis of disease pathogenesis. This is a pilot study on the neutrophils from the asymptomatic MMD and aberrantly expressed circRNAs in the profiling obtained by high-throughput microarray may help provide insights into MMD.