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Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder resulting from autoantibodies attacking components of the neuromuscular junction. Recent studies have implicated the aberrant expression of microRNAs (miRNAs) in the pathogenesis of MG; however, the underlying mechanisms remain largely un...

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Autores principales: Cao, Yuze, Wang, Jianjian, Zhang, Huixue, Tian, Qinghua, Chen, Lixia, Ning, Shangwei, Liu, Peifang, Sun, Xuesong, Lu, Xiaoyu, Song, Chang, Zhang, Shuai, Xiao, Bo, Wang, Lihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331476/
https://www.ncbi.nlm.nih.gov/pubmed/25705681
http://dx.doi.org/10.1155/2015/724715
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author Cao, Yuze
Wang, Jianjian
Zhang, Huixue
Tian, Qinghua
Chen, Lixia
Ning, Shangwei
Liu, Peifang
Sun, Xuesong
Lu, Xiaoyu
Song, Chang
Zhang, Shuai
Xiao, Bo
Wang, Lihua
author_facet Cao, Yuze
Wang, Jianjian
Zhang, Huixue
Tian, Qinghua
Chen, Lixia
Ning, Shangwei
Liu, Peifang
Sun, Xuesong
Lu, Xiaoyu
Song, Chang
Zhang, Shuai
Xiao, Bo
Wang, Lihua
author_sort Cao, Yuze
collection PubMed
description Myasthenia gravis (MG) is a neuromuscular autoimmune disorder resulting from autoantibodies attacking components of the neuromuscular junction. Recent studies have implicated the aberrant expression of microRNAs (miRNAs) in the pathogenesis of MG; however, the underlying mechanisms remain largely unknown. This study aimed to identify key genes regulated by miRNAs in MG. Six dysregulated pathways were identified through differentially expressed miRNAs and mRNAs in MG, and significant crosstalk was detected between five of these. Notably, crosstalk between the “synaptic long-term potentiation” pathway and four others was mediated by five genes involved in the MAPK signaling pathway. Furthermore, 14 key genes regulated by miRNAs were detected, of which six—MAPK1, RAF1, PGF, PDGFRA, EP300, and PPP1CC—mediated interactions between the dysregulated pathways. MAPK1 and RAF1 were responsible for most of this crosstalk (80%), likely reflecting their central roles in MG pathogenesis. In addition, most key genes were enriched in immune-related local areas that were strongly disordered in MG. These results provide new insight into the pathogenesis of MG and offer new potential targets for therapeutic intervention.
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spelling pubmed-43314762015-02-22 Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis Cao, Yuze Wang, Jianjian Zhang, Huixue Tian, Qinghua Chen, Lixia Ning, Shangwei Liu, Peifang Sun, Xuesong Lu, Xiaoyu Song, Chang Zhang, Shuai Xiao, Bo Wang, Lihua Biomed Res Int Research Article Myasthenia gravis (MG) is a neuromuscular autoimmune disorder resulting from autoantibodies attacking components of the neuromuscular junction. Recent studies have implicated the aberrant expression of microRNAs (miRNAs) in the pathogenesis of MG; however, the underlying mechanisms remain largely unknown. This study aimed to identify key genes regulated by miRNAs in MG. Six dysregulated pathways were identified through differentially expressed miRNAs and mRNAs in MG, and significant crosstalk was detected between five of these. Notably, crosstalk between the “synaptic long-term potentiation” pathway and four others was mediated by five genes involved in the MAPK signaling pathway. Furthermore, 14 key genes regulated by miRNAs were detected, of which six—MAPK1, RAF1, PGF, PDGFRA, EP300, and PPP1CC—mediated interactions between the dysregulated pathways. MAPK1 and RAF1 were responsible for most of this crosstalk (80%), likely reflecting their central roles in MG pathogenesis. In addition, most key genes were enriched in immune-related local areas that were strongly disordered in MG. These results provide new insight into the pathogenesis of MG and offer new potential targets for therapeutic intervention. Hindawi Publishing Corporation 2015 2015-02-01 /pmc/articles/PMC4331476/ /pubmed/25705681 http://dx.doi.org/10.1155/2015/724715 Text en Copyright © 2015 Yuze Cao et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cao, Yuze
Wang, Jianjian
Zhang, Huixue
Tian, Qinghua
Chen, Lixia
Ning, Shangwei
Liu, Peifang
Sun, Xuesong
Lu, Xiaoyu
Song, Chang
Zhang, Shuai
Xiao, Bo
Wang, Lihua
Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title_full Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title_fullStr Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title_full_unstemmed Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title_short Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis
title_sort detecting key genes regulated by mirnas in dysfunctional crosstalk pathway of myasthenia gravis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331476/
https://www.ncbi.nlm.nih.gov/pubmed/25705681
http://dx.doi.org/10.1155/2015/724715
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