Identification of Novel Key Genes and Pathways in Multiple Sclerosis Based on Weighted Gene Coexpression Network Analysis and Long Noncoding RNA-Associated Competing Endogenous RNA Network

Abstract

Objective. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by chronic inflammation and demyelination. This study is aimed at identifying crucial genes and molecular pathways involved in MS pathogenesis. Methods. Raw data in GSE52139 were collected from the Gene Expression Omnibus. The top 50% expression variants were subjected to weighted gene coexpression network analysis (WGCNA), and the key module associated with MS occurrence was identified. A long noncoding RNA- (lncRNA-) associated competing endogenous RNA (ceRNA) network was constructed in the key module. The hub gene candidates were subsequently verified in an individual database. Results. Of the 18 modules obtained, the cyan module was designated as the key module. The established ceRNA network was composed of seven lncRNAs, 45 mRNAs, and 21 microRNAs (miRNAs), and the FAM13A-AS1 was the lncRNA with the highest centrality. Functional assessments indicated that the genes in the cyan module primarily gathered in ribosome-related functional terms. Interestingly, the targeted mRNAs of the ceRNA network enriched in diverse categories. Moreover, highly expressed CYBRD1, GNG12, and SMAD1, which were identified as hub genes, may be associated with "valine leucine and isoleucine degradation,""base excision repair,"and "fatty acid metabolism,"respectively, according to the results of single gene-based genomes and gene set enrichment analysis (GSEA). Conclusions. Combined with the WGCNA and ceRNA network, our findings provide novel insights into the pathogenesis of MS. The hub genes discovered herein might also serve as novel biomarkers that correlate with the development and management of MS.