Network and Pathway-Based Analysis of Single-Nucleotide Polymorphism of miRNA in Temporal Lobe Epilepsy

Mol Neurobiol. 2019 Oct;56(10):7022-7031. doi: 10.1007/s12035-019-1584-4. Epub 2019 Apr 9.

Abstract

Temporal lobe epilepsy (TLE) is a complex disease with its pathogenetic mechanism still unclear. Single-nucleotide polymorphisms (SNPs) of miRNA (miRSNPs) are SNPs located on miRNA genes or target sites of miRNAs, which have been proved to be associated with neuropsychic disease development by interfering with miRNA-mediated regulatory function. In this study, we integrated TLE-related risk genes and risk pathways multi-dimensionally based on public data resources. Furthermore, we systematically screened candidate functional miRSNPs for TLE and constructed a TLE-associated pathway-based miRSNP switching network, which included 92 miRNAs that target 12 TLE risk pathways. Moreover, we dissected thoroughly the correlation between 5 risk genes of 4 risk pathways and TLE development. Additionally, the biological function of several candidate miRSNPs were validated by luciferase reporter assay. In silico approach facilitates to select potential "miRSNP-miRNA-risk gene-pathway" axis for experimental validation, which provided new insights into the mechanism of miRSNPs as potential genetic risk factors of TLE.

Keywords: Network; Pathway; Risk gene; Temporal lobe epilepsy (TLE); miRSNP.

MeSH terms

  • Base Sequence
  • Epilepsy, Temporal Lobe / genetics*
  • Gene Regulatory Networks*
  • Genes, Reporter
  • Genetic Predisposition to Disease*
  • Humans
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors

Substances

  • MicroRNAs
  • Luciferases