Deep Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous Malformations

Background Deregulation of circulating microRNAs (miRNAs) is always associated with development and progression of human diseases. We aimed to assess whether patients with brain arteriovenous malformations (BAVMs) possess a distinct miRNA signature compared with healthy subjects. Methods Three patients with unruptured BAVMs and 3 normal control subjects were recruited as case and control groups. Peripheral blood was collected, and miRNA signature was obtained by next-generation sequencing, followed by comparative, functional, and network analyses. Quantitative reverse transcription polymerase chain reaction was performed to validate expression of specific miRNAs. Results Deep sequencing detected 246 differentially expressed miRNAs in blood samples of patients with BAVMs compared with normal control subjects. For the top 5 miRNAs, 946 target genes were predicted, and a BAVM-specific miRNA-target gene regulatory network was constructed. Functional annotation suggested that 15 of the predicted miRNA-targeted genes were involved in vascular endothelial growth factor signaling, in which 3 critical miRNAs were involved: miR-7-5p, miR-199a-5p, and miR-200b-3p. Conclusions We explored the miRNA expression signature of BAVMs, which will provide an important foundation for future studies on the regulation of miRNAs involved in BAVMs.