DNA Methylation Regulates Gene Expression in Intracranial Aneurysms

World Neurosurg. 2017 Sep:105:28-36. doi: 10.1016/j.wneu.2017.04.064. Epub 2017 Apr 19.

Abstract

Background: Different gene expression profiles are observed in intracranial aneurysm tissues. Understanding these genes and what regulates their expression will provide insight into the pathogenesis of intracranial aneurysms. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms.

Methods: We compared 20 intracranial aneurysm tissue specimens with 20 matched specimens from the superficial temporal artery as controls. We identified the gene expression profiles in these samples using the GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications using the Infinium HumanMethylation450 BeadChip Kit.

Results: A total of 11,022 differentially methylated sites between aneurysm tissues and matched control tissues were identified, and 2142 differentially expressed gene transcripts were detected based on the 2 gene expression profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and verification analysis showed that the MYH11, LIFR, and TLR4 genes were associated with the occurrence and development of intracranial aneurysms. These genes mainly encode cell adhesion molecules or are involved in the NF-κB, JAK-STAT, and ERK/JNK signaling pathways.

Conclusions: In the development of intracranial aneurysms, DNA methylation plays an important role in the regulation of genetic expression involved in immune and inflammatory reactions, cell function, cell maintenance, and cell signal transduction.

Keywords: DNA methylation; Gene expression profile; Intracranial aneurysm; Microarray analysis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • DNA Methylation / genetics*
  • Female
  • Humans
  • Intracranial Aneurysm / genetics*
  • Intracranial Aneurysm / pathology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • Temporal Arteries
  • Transcriptome
  • Young Adult