title: Systems biology of myasthenia gravis, integration of aberrant lncRNA and mRNA expression changes.
abstract: BACKGROUND
  A novel class of transcripts, long non-coding RNAs (lncRNAs), has recently emerged as a key player in several biological processes, and important roles for these molecules have been reported in a number of complex human diseases, such as autoimmune diseases, neurological disorders, and various cancers. However, the aberrant lncRNAs implicated in myasthenia gravis (MG) remain unknown. The aim of the present study was to explore the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) and examine mRNA regulatory relationship networks among MG patients with or without thymoma.
  
  
  METHODS
  Microarray assays were performed, and the outstanding differences between lncRNAs or mRNA expression were verified through RT-PCR. The lncRNAs functions were annotated for the target genes using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The potential regulatory relationships between the lncRNAs and target genes were analyzed using the 'cis' and 'trans' model. Outstanding lncRNAs were organized to generate a TF-lncRNA-gene network using Cytoscape software.
  
  
  RESULTS
  The lncRNA and mRNA expression profile analysis revealed subsets of differentially expressed genes in MG patients with or without thymoma. A total of 12 outstanding dysregulated expression lncRNAs, such as lncRNA oebiotech_11933, were verified through real-time PCR. Several GO terms including the cellular response to interferon-γ, platelet degranulation, chemokine receptor binding and cytokine interactions were very important in MG pathogenesis. The chromosome locations of some lncRNAs and associated co-expression genes were demonstrated using 'cis' analysis. The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression. The outstanding lncRNAs in each group were implicated in the regulation of the TF-lncRNA-target gene network.
  
  
  CONCLUSIONS
  The results of the present study provide a perspective on lncRNA expression in MG. We identify a subset of aberrant lncRNAs and mRNAs as potential biomarkers for the diagnosis of MG. The GO and KEGG pathway analysis provides an annotation to determine the functions of these lncRNAs. The results of the 'cis' and 'trans' analyses provide information concerning the modular regulation of lncRNAs.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. luozhaohui_xy@126.com.
authors.forename: ZhaoHui
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. 454382507@qq.com.|Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, 350001, China. 454382507@qq.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. 294350250@qq.com.
authors.forename: XiaoFang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. mchuanlow@gmail.com.
authors.forename: MengChuan
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. 183752665@qq.com.
authors.forename: LiQun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. yuebei57@gmail.com.
authors.forename: YueBei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. xiaobo_xy@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. yangh69@126.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D049490:Systems Biology; D013945:Thymoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D062085:RNA, Long Noncoding; D012333:RNA, Messenger