Kai Qian1,2, Jia-Xin Xu3, Yi Deng4, Hao Peng2, Jun Peng2, Chun-Mei Ou5, Zu Liu3, Li-Hong Jiang2, Yong-Hang Tai6. 1. Faculty of Life and Biotechnology, Kunming University of Science and Technology, Kunming, China. 2. Department of Thoracic Surgery, Institute of The First People's Hospital of Yunnan Province, Kunming, China. 3. Department of Cardiovascular surgery, Yan' an Affiliated Hospital of Kunming Medical University, Kunming, China. 4. Department of Oncology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China. 5. Department of Cardiovascular surgery, Institute of the First People's Hospital of Yunnan Province, Kunming, China. 6. School of Electronic Information in the Yunnan Normal University, Kunming, China.
Abstract
BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder causing muscle weakness and characterized by a defect in synaptic transmission at the neuromuscular junction. The pathogenesis of this disease remains unclear. We aimed to predict the key signaling pathways of genetic variants and miRNAs in the pathogenesis of MG, and identify the key genes among them. METHODS: We searched published information regarding associated single nucleotide polymorphisms (SNPs) and differentially-expressed miRNAs in MG cases. We search of SNPs and miRNAs in literature databases about MG, then we used bioinformatic tools to predict target genes of miRNAs. Moreover, functional enrichment analysis for key genes was carried out utilizing the Cytoscape-plugin, known as ClueGO. These key genes were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then a miRNA-target gene regulatory network was established to screen key genes. RESULTS: Five genes containing SNPs associated with MG risk were involved in the inflammatory bowel disease (IBD) signaling pathway, and FoxP3 was the key gene. MAPK1, SMAD4, SMAD2 and BCL2 were predicted to be targeted by the 18 miRNAs and to act as the key genes in adherens, junctions, apoptosis, or cancer-related pathways respectively. These five key genes containing SNPs or targeted by miRNAs were found to be involved in negative regulation of T cell differentiation. CONCLUSIONS: We speculate that SNPs cause the genes to be defective or the miRNAs to downregulate the factors that subsequently negatively regulate regulatory T cells and trigger the onset of MG. 2020 Gland Surgery. All rights reserved.
BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder causing muscle weakness and characterized by a defect in synaptic transmission at the neuromuscular junction. The pathogenesis of this disease remains unclear. We aimed to predict the key signaling pathways of genetic variants and miRNAs in the pathogenesis of MG, and identify the key genes among them. METHODS: We searched published information regarding associated single nucleotide polymorphisms (SNPs) and differentially-expressed miRNAs in MG cases. We search of SNPs and miRNAs in literature databases about MG, then we used bioinformatic tools to predict target genes of miRNAs. Moreover, functional enrichment analysis for key genes was carried out utilizing the Cytoscape-plugin, known as ClueGO. These key genes were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then a miRNA-target gene regulatory network was established to screen key genes. RESULTS: Five genes containing SNPs associated with MG risk were involved in the inflammatory bowel disease (IBD) signaling pathway, and FoxP3 was the key gene. MAPK1, SMAD4, SMAD2 and BCL2 were predicted to be targeted by the 18 miRNAs and to act as the key genes in adherens, junctions, apoptosis, or cancer-related pathways respectively. These five key genes containing SNPs or targeted by miRNAs were found to be involved in negative regulation of T cell differentiation. CONCLUSIONS: We speculate that SNPs cause the genes to be defective or the miRNAs to downregulate the factors that subsequently negatively regulate regulatory T cells and trigger the onset of MG. 2020 Gland Surgery. All rights reserved.
Authors: Yingkai Li; Jeffrey T Guptill; Melissa A Russo; James F Howard; Janice M Massey; Vern C Juel; Lisa D Hobson-Webb; Doug Emmett; Manisha Chopra; Shruti Raja; Weibin Liu; John S Yi Journal: J Neuroimmunol Date: 2020-05-27 Impact factor: 3.478
Authors: Andrea C Kakouri; Christina Votsi; Marios Tomazou; George Minadakis; Evangelos Karatzas; Kyproula Christodoulou; George M Spyrou Journal: Int J Mol Sci Date: 2020-09-14 Impact factor: 5.923