Construction of a lncRNA–miRNA–mRNA Network to Determine the Key Regulators of the Th1/Th2 Imbalance in Multiple Sclerosis

Azari, Hanieh; Karimi, Elham; Shekari, Mohammad; Tahmasebi, Ahmad; Nikpoor, Amin Reza; Negahi, Ahmad Agha; Sanadgol, Nima; Mousavi, Pegah

doi:10.2217/epi-2021-0296

Cited by 19 publications

(12 citation statements)

References 56 publications

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“…Furthermore, scientists found that NEAT1 regulates the expression of proinflammatory factors through the MAPK pathway [ 105 ]. Moreover, similar to the findings in MS, a role of NEAT1 in the Th1/Th2 imbalance was recently described in SLE [ 106 , 107 ]. PBMCs from 97 SLE patients and 50 healthy volunteers were studied, and higher expression of NEAT1 and a lower Th1/Th2 ratio were observed in the SLE group, which reflected upregulation of IL4 and downregulation of IFNγ [ 106 ].…”

Section: Autoimmune and Neurodegenerative Disorder Pathomechanisms Ca...supporting

confidence: 84%

“…RUNX3 regulates the production of IFNγ in Th1 cells and IL4 in Th2 cells via TBX21 and GATA3, respectively. Dysregulation of the levels of both these miRNAs and their downstream targets consequently leads to an IFNγ(Th1)/IL4(Th2) imbalance, which plays an important role in the regulation of inflammation in MS [ 107 ].…”

Section: Autoimmune and Neurodegenerative Disorder Pathomechanisms Ca...mentioning

confidence: 99%

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Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

Plewka

Raczyńska

2022

Mol Neurobiol

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Long intergenic noncoding RNAs (lincRNAs) are a class of independently transcribed molecules longer than 200 nucleotides that do not overlap known protein-coding genes. LincRNAs have diverse roles in gene expression and participate in a spectrum of biological processes. Dysregulation of lincRNA expression can abrogate cellular homeostasis, cell differentiation, and development and can also deregulate the immune and nervous systems. A growing body of literature indicates their important and multifaceted roles in the pathogenesis of several different diseases. Furthermore, certain lincRNAs can be considered potential therapeutic targets and valuable diagnostic or prognostic biomarkers capable of predicting the onset of a disease, its degree of activity, or the progression phase. In this review, we discuss possible mechanisms and molecular functions of lincRNAs in the pathogenesis of selected autoimmune and neurodegenerative disorders: multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. This summary can provide new ideas for future research, diagnosis, and treatment of these highly prevalent and devastating diseases.

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Section: Autoimmune and Neurodegenerative Disorder Pathomechanisms Ca...supporting

confidence: 84%

Section: Autoimmune and Neurodegenerative Disorder Pathomechanisms Ca...mentioning

confidence: 99%

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

Plewka

Raczyńska

2022

Mol Neurobiol

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“…GATA3 is a transcription factor required for Th2 cell differentiation, which promotes the development of Th2 cells and prevents the proliferation of Th1 cells. Studies had reported that the expression of GATA3 in peripheral blood of MS patients decreased, while the increase of its expression reduced the severity of EAE ( 44 , 45 ). PI3K is widely expressed and participates in multiple inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren’s Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data

et al. 2022

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ObjectiveThis study aimed to explore the shared mechanism and candidate drugs of multiple sclerosis (MS) and Sjögren’s syndrome (SS).MethodsMS- and SS-related susceptibility genes and differentially expressed genes (DEGs) were identified by bioinformatics analysis based on genome-wide association studies (GWAS) and transcriptome data from GWAS catalog and Gene Expression Omnibus (GEO) database. Pathway enrichment, Gene Ontology (GO) analysis, and protein–protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through Comparative Toxicogenomics Database (CTD), DrugBank database, and Drug–Gene Interaction (DGI) Database. The target genes of approved/investigational drugs for MS and SS were obtained through DrugBank and compared with the common susceptibility genes.ResultsBased on GWAS data, we found 14 hub common susceptibility genes (HLA-DRB1, HLA-DRA, STAT3, JAK1, HLA-B, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB5, HLA-DPA1, HLA-DPB1, TYK2, IL2RA, and MAPK1), with 8 drugs targeting two or more than two genes, and 28 common susceptibility pathways, with 15 drugs targeting three or more than three pathways. Based on transcriptome data, we found 3 hub common DEGs (STAT1, GATA3, PIK3CA) with 3 drugs and 10 common risk pathways with 435 drugs. “JAK-STAT signaling pathway” was included in common susceptibility pathways and common risk pathways at the same time. There were 133 overlaps including JAK-STAT inhibitors between agents from GWAS and transcriptome data. Besides, we found that IL2RA and HLA-DRB1, identified as hub common susceptibility genes, were the targets of daclizumab and glatiramer that were used for MS, indicating that daclizumab and glatiramer may be therapeutic for SS.ConclusionWe observed the shared mechanism of MS and SS, in which JAK-STAT signaling pathway played a vital role, which may be the genetic and molecular bases of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors were potential therapies for MS and SS, especially for their comorbidity.

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“…Common target genes among either anxiolytic or anxiogenic highlighted miR are determined via the miRDB database, and their potential protein-protein interaction (PPI) network and key hub genes were constructed using the STRING database version 11.0 ( , accessed on 18 July 2022) with confidence scores of ≥0.9 as a threshold [ 13 , 14 ]. Moreover, specific interactions of each highlighted miR with the mRNA sequence of common target genes were also predicted by the TargetScan database to confirm better the possibility of miR-mRNA interactions ( , accessed on 21 August 2022) [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

et al. 2023

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Anxiety-related disorders (ARDs) are chronic neuropsychological diseases and the sixth leading cause of disability in the world. As dysregulation of microRNAs (miRs) are observed in the pathological course of neuropsychiatric disorders, the present study aimed to introduce miRs that underlie anxiety processing in the brain. First, we collected the experimentally confirmed anxiety-related miRNAs (ARmiRs), predicted their target transcripts, and introduced critical cellular pathways with key commune hub genes. As a result, we have found nine anxiolytic and ten anxiogenic ARmiRs. The anxiolytic miRs frequently target the mRNA of Acyl-CoA synthetase long-chain family member 4 (Acsl4), AFF4-AF4/FMR2 family member 4 (Aff4), and Krüppel like transcription factor 4 (Klf4) genes, where miR-34b-5p and miR-34c-5p interact with all of them. Moreover, the anxiogenic miRs frequently target the mRNA of nine genes; among them, only two miR (miR-142-5p and miR-218-5p) have no interaction with the mRNA of trinucleotide repeat-containing adaptor 6B (Tnrc6b), and miR-124-3p interacts with all of them where MAPK is the main signaling pathway affected by both anxiolytic and anxiogenic miR. In addition, the anxiolytic miR commonly target E2F transcription factor 5 (E2F5) in the TGF-β signaling pathway, and the anxiogenic miR commonly target Ataxin 1 (Atxn1), WASP-like actin nucleation promoting factor (Wasl), and Solute Carrier Family 17 Member 6 (Slc17a6) genes in the notch signaling, adherence junction, and synaptic vesicle cycle pathways, respectively. Taken together, we conclude that the most important anxiolytic (miR-34c, Let-7d, and miR-17) and anxiogenic (miR-19b, miR-92a, and 218) miR, as hub epigenetic modulators, potentially influence the pathophysiology of anxiety, primarily via interaction with the MAPK signaling pathway. Moreover, the role of E2F5 as a novel putative target for anxiolytic miRNAs in ARDs disorders deserves further exploration.

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Construction of a lncRNA–miRNA–mRNA Network to Determine the Key Regulators of the Th1/Th2 Imbalance in Multiple Sclerosis

Cited by 19 publications

References 56 publications

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren’s Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

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