Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating and degenerative disease with unknown etiology. Inappropriate response of T-cells to myelin antigens has an essential role in the pathophysiology of MS. The clinical and pathophysiological complications of MS necessitate identification of potential molecular targets to understand the pathogenic events of MS. Since the functions and regulatory mechanisms of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in MS are yet uncertain, we conducted a bioinformatics analysis to explain the lncRNA-associated ceRNA axes to clarify molecular regulatory mechanisms involved in T-cells responses in MS. Two microarray datasets of peripheral blood T-cell from subjects with relapsing-remitting MS and matched controls containing data about miRNAs (GSE43590), mRNAs and lncRNAs (GSE43591) were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) were identified by the limma package of the R software. Protein-protein interaction (PPI) network and module were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) Cytoscape plugin, respectively. Using DIANA-LncBase and miRTarBase, the lncRNA-associated ceRNA axes was constructed. We conducted a Pearson correlation analysis and selected the positive correlations among the lncRNAs and mRNAs in the ceRNA axes. Lastly, DEmRNAs pathway enrichment was conducted by the Enrichr tool. A ceRNA regulatory relationship among Small nucleolar RNA host gene 1 (SNHG1), hsa-miR-197-3p, YOD1 deubiquitinase (YOD1) and zinc finger protein 101 (ZNF101) and downstream connected genes was identified. Pathway enrichment analysis showed that DEmRNAs were enriched in “Protein processing in endoplasmic reticulum” and “Herpes simplex virus 1 infection” pathways. To our knowledge, this would be the first report of a possible role of SNHG1/hsa-miR-197-3p/YOD1/ZNF101 axes in the pathogenesis of MS. This research remarks on the significance of ceRNAs and prepares new perceptions for discovering the molecular mechanism of MS.
Highlights
Multiple sclerosis (MS) is the most frequent cause of nontraumatic neurological disability in young adult people [1]
We utilized a public database to download the expression profiles of peripheral blood T-cells from relapsing-remitting MS (RRMS) patients to assess the DEmiRNAs, DElncRNAs, and DEmRNAs in RRMS and normal samples and construct lncRNAmiRNA-mRNA regulatory axes. According to these competing endogenous RNAs (ceRNAs) axes and long non-coding RNAs (lncRNAs)-mRNA co-expression relationships, we found the lncRNA-miRNA-mRNA axes consisting of one lncRNA (SNHG1), one miRNA, and two mRNAs (YOD1 and ZNF101)
The results showed that DEmRNAs that were in the ceRNA axes were enriched in “Protein processing in endoplasmic reticulum” and “Herpes simplex virus 1 infection” pathways, respectively
Summary
Multiple sclerosis (MS) is the most frequent cause of nontraumatic neurological disability in young adult people [1]. Estimates indicate that a total of 2.8 million individuals with MS live around the world (35.9 per 100,000 population) [2]. In this degenerative disorder, the central nervous system is demyelinated through the mediation of the immune system. MS presents in four clinical types: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS). RRMS is the most common subtype, which is represented by acute attacks (relapses) and partially or fully recovered phases (remission) [3]. The causes and etiologies underlie MS are not completely apprehended, there are proofs that it originates from multiple factors involving central and peripheral immunological tolerance mechanisms. LncRNAs have major contributions to complex disorders (e.g., MS) through functioning as competing endogenous RNAs (ceRNAs) [8]
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