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Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2017 Feb; Vol. 39 (2), pp. 268-278. Date of Electronic Publication: 2017 Jan 11. - Publication Year :
- 2017
-
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.
- Subjects :
- Computational Biology methods
Databases, Nucleic Acid
Gene Expression Profiling
Humans
Molecular Sequence Annotation
Multigene Family
Myasthenia Gravis metabolism
Signal Transduction drug effects
Transcriptome
Drug Discovery
Drug Repositioning
Gene Expression Regulation drug effects
Gene Regulatory Networks drug effects
MicroRNAs genetics
Myasthenia Gravis drug therapy
Myasthenia Gravis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28075449
- Full Text :
- https://doi.org/10.3892/ijmm.2017.2853