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

World Neurosurg. 2018 Jul:115:e570-e579. doi: 10.1016/j.wneu.2018.04.097. Epub 2018 Apr 22.

Abstract

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.

Keywords: Brain arteriovenous malformations; VEGF signaling; miRNAs.

MeSH terms

  • Adolescent
  • Adult
  • Arteriovenous Fistula / blood*
  • Arteriovenous Fistula / genetics*
  • Biomarkers / blood
  • Child
  • Female
  • Humans
  • Intracranial Arteriovenous Malformations / blood*
  • Intracranial Arteriovenous Malformations / genetics*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Sequence Analysis, RNA / methods*
  • Young Adult

Substances

  • Biomarkers
  • MicroRNAs