Integrated Analysis and Identification of CSF-Derived Risk miRNAs and Pivotal Genes in Multiple Sclerosis

Yingchao Su1, Zhihui Li2, Xinming Rang1

  • 1Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin, 150086, China.

Insights

This study identifies key microRNAs (miRNAs) and genes in cerebrospinal fluid (CSF) linked to multiple sclerosis (MS). These findings highlight potential biomarkers and therapeutic targets for MS pathogenesis.

Area of Science:

  • Neuroimmunology
  • Genomics
  • Biomarker Discovery

Background:

  • Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, primarily in young adults.
  • MicroRNAs (miRNAs) in cerebrospinal fluid (CSF) are increasingly recognized as potential biomarkers for MS.
  • Comprehensive analysis of CSF miRNAs and their target genes in MS is currently lacking.

Purpose of the Study:

  • To identify aberrantly expressed miRNAs in the CSF of MS patients.
  • To elucidate the target genes, pathways, and molecular mechanisms involved in MS pathogenesis.
  • To discover potential diagnostic biomarkers and therapeutic targets for MS.

Main Methods:

  • Manual literature search to collect MS-related CSF miRNAs.
  • Utilized online databases for screening immune-related target genes.
  • Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
  • Constructed pathway crosstalk, pathway-gene networks, and protein-protein interaction (PPI) networks.
  • Validated pivotal genes using transcriptomic datasets from ArrayExpress.

Main Results:

  • Identified 21 MS-related CSF miRNAs, 469 MS-related genes, and 14 high-risk pathways.
  • Discovered 27 critical MS-related genes involved in high-risk pathways, leading to the identification of pivotal genes.
  • Determined miR-150, miR-328, and miR-34c-5p as risk miRNAs regulating pivotal genes MAPK1, AKT1, and VEGFA.
  • VEGFA was significantly decreased in CSF cells of MS patients, validated by transcriptomic data.

Conclusions:

  • The study identified specific miRNAs (miR-150, miR-328, miR-34c-5p) and genes (MAPK1, AKT1, VEGFA) associated with MS pathogenesis.
  • VEGFA's decreased expression in MS patient CSF cells suggests its role in the disease.
  • These findings offer potential biomarkers and therapeutic targets for multiple sclerosis.

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