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      LncRNA and mRNA expression associated with myasthenia gravis in patients with thymoma

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          Abstract

          Objective

          Pathological alterations of the thymus are observed in the majority of patients with myasthenia gravis (MG). To explore the potential mechanisms of these alterations, we performed a transcriptome analysis and measured co‐expression of aberrant long non‐coding RNAs (lncRNAs) and messenger RNAs (mRNAs).

          Methods

          RNA was extracted from eight patients with thymoma, five of whom had MG. Transcriptome profiles were acquired through mRNA and lncRNA microarray analysis. Quantitative reverse transcription polymerase chain reaction was used to verify the results of the microarray analysis. LncRNAs co‐expressed with mRNA were analyzed with Pearson's coefficient. Next, cis‐regulated and trans‐regulated target genes were predicted. The functions of aberrant lncRNAs were explored on the basis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of target mRNAs.

          Results

          The comparative microarray analysis identified 4360 lncRNAs and 2545 mRNAs with significant differential expression. The most significant GO enrichment terms were phosphoric ester hydrolase activity, phosphatase activity, and hydrolase activity, which were assigned as molecular functions. Regulation of endosome size was the most significant GO enrichment term assigned as a biological process, and Golgi apparatus was the most significant GO enrichment term assigned as cellular component. The reliability prediction terms of KEGG included calcium signaling pathway, glycosphingolipid biosynthesis, and caffeine metabolism.

          Conclusion

          MG‐positive thymoma is associated with overactive biological processes and molecular functions, especially dephosphorylation and hydrolysis, which may affect thymocyte survival during selection in the thymus.

          Abstract

          MG‐positive thymoma is associated with overactive biological processes and molecular functions, especially dephosphorylation and hydrolysis, which may affect thymocyte survival during selection in the thymus.

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          Most cited references24

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          Genome regulation by long noncoding RNAs.

          The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs), provides an important new perspective on the centrality of RNA in gene regulation. Here, we discuss genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, lncRNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs for proper gene control across all kingdoms of life.
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            Long non-coding RNAs in the regulation of the immune response

            Highlights • Widespread changes in lncRNA expresssion are associated with the immune response. • lncRNAs regulate the inflammatory response following activation of innate immunity. • lncRNAs regulate T cell differentiation and migration. • The action of long non-coding RNAs is mediated via diverse mechanisms.
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              The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes.

              The thymus plays distinct roles in the pathogenesis of the different Myasthenia gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late onset MG, respectively. By contrast, the thymus is presumably not related to MG that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has not been their standard treatment. This review aims to give an update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal T cell selection and activation, the role of thymic myoid cells, the autoimmune regulator (AIRE) and regulatory T cells. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                yulei118@163.com
                huilee@vip.sina.com
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                12 November 2021
                January 2022
                : 13
                : 1 ( doiID: 10.1111/tca.v13.1 )
                : 15-23
                Affiliations
                [ 1 ] Department of Thoracic Surgery, Beijing Tongren Hospital Capital Medical University Beijing China
                [ 2 ] Department of Thoracic Surgery Beijing Chaoyang Hospital, Capital Medical University Beijing China
                Author notes
                [*] [* ] Correspondence

                Hui Li, Department of Thoracic Surgery, Beijing, Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

                Email: huilee@ 123456vip.sina.com

                Lei Yu, Department of Thoracic Surgery, Beijing Tongren Hospital, Capital Medical, University, Beijing 100730, China.

                Email: yulei118@ 123456163.com

                Author information
                https://orcid.org/0000-0002-1511-3564
                https://orcid.org/0000-0003-0103-1872
                Article
                TCA14201
                10.1111/1759-7714.14201
                8720629
                34773374
                ff5a5ed5-93ac-43b3-a8cb-723a00a2f2bf
                © 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 06 October 2021
                : 06 July 2021
                : 07 October 2021
                Page count
                Figures: 8, Tables: 1, Pages: 9, Words: 3767
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                January 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.7.0 mode:remove_FC converted:02.01.2022

                long non‐coding rna,microarray analysis,mrna,myasthenia gravis,thymoma

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