Identification and functional analysis of specific MS risk miRNAs and their target genes

Mult Scler Relat Disord. 2020 Jun:41:102044. doi: 10.1016/j.msard.2020.102044. Epub 2020 Mar 5.

Abstract

Background: It has been widely acknowledged that abnormal expression of microRNAs (miRNAs) may lead to the occurrence and development of MS through regulating target genes. Currently, only few studies have comprehensively evaluated the function and relationship between MS-related miRNAs and their target genes.

Methods: Differentially expressed miRNAs in MS patients' serum and plasma were selected by reviewing numerous literatures manually. Then, thousands of target genes were screened by several online databases, of which 899 MS-related genes were further identified. Gene ontology, protein-protein interaction and KEGG pathway analysis were used to determine high-risk pathways and MS risk genes. Transcriptomic datasets from GEO was analyzed to evaluate these risk genes.

Results: 28 MS-related miRNAs were extracted. MiR-30e, miR-93, miR-155 were identified as the most crucial miRNAs through targeting hub genes: PIK3CA, PIK3R1, PIK3R2 and MAPK8. Seven immune pathways were screened out according to KEGG pathway analysis. Six transcriptomic datasets were used to evaluate results, and PIK3CA was differentially expressed in MS patients compared with healthy donors.

Conclusions: According to our research, MS-related miRNAs and their target genes of MS were identified and comprehensively evaluated. This work may provide a new insight for discovering pathogenesis and possible biomarkers of MS in future studies.

Keywords: Bioinformatics; Multiple sclerosis; Pathways; Risk genes; miRNAs.

MeSH terms

  • Gene Expression Profiling*
  • Gene Ontology
  • Humans
  • MAP Kinase Signaling System / genetics
  • Metabolic Networks and Pathways / genetics*
  • MicroRNAs / blood*
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Interaction Maps
  • Signal Transduction / genetics*

Substances

  • MIRN155 microRNA, human
  • MIRN30b microRNA, human
  • MIRN93 microRNA, human
  • MicroRNAs