title: Detecting key genes regulated by miRNAs in dysfunctional crosstalk pathway of myasthenia gravis.
abstract: 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.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China ; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yuze
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Huixue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Shangwei
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Peifang
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009469:Neuromuscular Junction / Q000276:immunology / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D001323:Autoantibodies; D035683:MicroRNAs; D012333:RNA, Messenger