Abstract
BackgroundA 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.MethodsMicroarray 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.ResultsThe 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0087-z) contains supplementary material, which is available to authorized users.
Highlights
A novel class of transcripts, long non-coding RNAs, 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
Results long non-coding RNAs (lncRNAs) and mRNA expression profile in myasthenia gravis (MG) To investigate the expression levels of lncRNAs associated with MG with or without thymoma, lncRNA and mRNA microarray analyses were performed on the Peripheral blood mononuclear cell (PBMC) of MG patients
Using dendrogram-based methods for clustering, the samples were further separated into two subgroups through hierarchical clustering based on similar expression patterns, and the results indicate that the expression of these lncRNAs and mRNAs was significantly different in MG patients with or without thymoma
Summary
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. 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. Myasthenia gravis (MG) is a T and B cell-mediated autoimmune disease of the neuromuscular junction; cytokines and chemokines may play a crucial role in the pathogenesis and perpetuation of this disease [1,2,3]. Other targets, such as muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4), have been described [3]. The thymus has long been considered to be closely associated with the pathogenesis of MG, and some studies have suggested that MG autoimmune reactions originate in the thymus [7,10]. Additional studies concerning the role of the thymus gland in the pathogenesis of MG are required
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