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.

Multiple Sclerosis Stages and their Differentially Expressed Genes: A Bioinformatics Analysis

“…Furthermore, the treatment of these cells with a common MS therapy can restore the levels of some of these RNAs, suggesting that the dysregulated polyadenylation may have pathogenic consequences (LaCava et al ., 2005). A study by Hao et al ., (2022) also showed that hub genes targeted by long non-coding RNAs (lncRNAs) and competing endogenous RNAs (ceRNAs) functioned in ribosomal processes. In addition, gene set enrichment analysis also showed that highly expressed hub genes were associated with base excision repair.…”

Initial evaluation of LncRNA A2M-AS1 gene expression in multiple sclerosis patients

“…that by following similar signaling pathways, the possible and similar effect of this LncRNA in MS can also be addressed. Other mRNAs examined include: ZMAT3, CCDC113, CMPK1, MCC, KCNK2, KCTD15, PIM1, GJA1, TMED5, BMPR1B, WEE1, CYBRD1, MAPK1, CRKL, PHKA1, DICER1, SEMA7A, RRAGD, ABHD17C, TOB1, FOXP4, ADD3, CMTM4, TGFBR3, ARHGEF26, SEMA6D, PREX2, GABRB1, PDLIM5, HNRNPF, RHOQ, ANKFY1, USP46, MTSS1, UXS1, PPP2CB, NOTCH2, FGFRL1, ZNF711, ROCK1, GNG12, CTSA, SUN2, SMAD1, LONRF1 and from Among the key LncRNAs investigated in multiple sclerosis disease, we can mention C17orf82, BOLA3-AS1, RBM26-AS1, RBMS3-AS3, CRNDE, FAM13A-AS1, VENTXP1 according to the studies of Dr. Hao and colleagues in 2022 (22).…”

Novel regulatory role of non-coding RNAs in ankylosing spondylitis

“…Different RNAs will form multiple regulatory relationships, which will eventually form a ceRNA network. Currently, studies are being conducted on the pathogenesis of ceRNA-related diseases, and various ncRNAs (e.g., lncRNAs, miRNAs, circRNAs) and ceRNA networks constructed from differentially expressed ncRNAs have been shown to be related to the pathogenesis of various autoimmune diseases (20)(21)(22)(23), further illustrating the interconnection between different RNA molecules and the regulation of gene expression. The construction of ceRNA regulatory networks is of great importance to further understand the functions of ncRNAs.…”