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.

Yuehan Hao,Chenyang Zhao,Xiaoxue Xu,Shuang Xiong,Yu Fu,Miao He,Muneeb U Rehman

doi:10.1155/2022/9328160

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.

Highlights

The impairment of the immune response leads to the production of aberrant autoantibodies, which damage the immunological tolerance to self-antigens, contributing to several autoimmune disorders (ADs) [1]
Our study focused on the crucial gene group that is closely associated with the Multiple sclerosis (MS) clinical features generated using weighted gene coexpression network analysis (WGCNA) to explore the MS mechanism occurring in the spinal cord
The long noncoding RNA- (lncRNA-)associated competing endogenous RNA (ceRNA) network constructed in the key module revealed the regulatory role of Long noncoding RNAs (lncRNAs)

Summary

Introduction

The impairment of the immune response leads to the production of aberrant autoantibodies, which damage the immunological tolerance to self-antigens, contributing to several autoimmune disorders (ADs) [1]. Multiple sclerosis (MS) is the most prevalent AD, and patients with MS exhibit immune-mediated inflammation and neuronal sheath loss in the central nervous system. The onset of the disease is characterized by brain and spinal cord atrophy, which advances over the course of the disease. Spinal cord involvement turns MS into a frequent determinant of neurological disability. Several treatments have been applied to mitigate MS symptoms by modulating or suppressing the immune system, the deficiency of curative strategies remains an important issue that must be urgently solved. A comprehensive understanding of the molecular pathways and hub genes involved will be crucial for developing promising MS therapies

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Results

Discussion

Conclusion