title: Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis.
abstract: Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases. Based on these genes and miRNAs, we identified 41 MG risk pathways and 105 approved drugs that can affect these pathways. Some important MG-related pathways, such as hsa04060 (cytokine-cytokine receptor interaction) and hsa05200 (pathway in cancer), were found to be regulated by MG risk miRNAs and drugs. Furthermore, we constructed an miRNA-regulated drug-pathway network and identified miRNAs and drugs that synergistically regulate key MG pathways and biological processes. We developed a drug repurposing strategy to identify 25 drug repurposing candidates for MG; several of these drugs, such as rituximab, adalimumab, sunitinib, and muromonab, have the potential to be novel MG treatment drugs. This study provides novel insight into the pathogenesis of MG and potential drug candidates for MG were identified.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. 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, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. 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, P.R. 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, P.R. China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Si
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Shangwei
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. 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, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
mesh_terms: D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D055808:Drug Discovery; D058492:Drug Repositioning; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D035683:MicroRNAs