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      lncRNA:mRNA expression profile in CD4+ T cells from patients with Graves’ disease

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          Abstract

          Graves’ disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compared with healthy control CD4+ T cells. Quantitative PCR (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and clinical parameters. The microarray identified 164 lncRNAs and 93 mRNAs in GD CD4+ T cells differentially expressed compared to healthy control CD4+ T cells (fold change >2.0 and a P < 0.05). Further analysis consistently showed that the expression of HMlincRNA1474 ( P < 0.01) and TCONS_00012608 ( P < 0.01) was suppressed, while the expression of AK021954 ( P < 0.01) and AB075506 ( P < 0.01) was upregulated from initial GD patients. In addition, their expression levels were recovered in euthyroid GD patients and GD patients in remission. Moreover, these four aberrantly expressed lncRNAs were correlated with GD clinical parameters. Moreover, the areas under the ROC curve were 0.8046, 0.7579, 0.8115 for AK021954, AB075506, HMlincRNA1474, respectively. The present work revealed that differentially expressed lncRNAs were associated with GD, which might serve as novel biomarkers of GD and potential targets for GD treatment.

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          Most cited references43

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          Long non-coding RNAs: insights into functions.

          In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.
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            Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.

            There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
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              Non-coding RNA.

              The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have function. Although it has been generally assumed that most genetic information is transacted by proteins, recent evidence suggests that the majority of the genomes of mammals and other complex organisms is in fact transcribed into ncRNAs, many of which are alternatively spliced and/or processed into smaller products. These ncRNAs include microRNAs and snoRNAs (many if not most of which remain to be identified), as well as likely other classes of yet-to-be-discovered small regulatory RNAs, and tens of thousands of longer transcripts (including complex patterns of interlacing and overlapping sense and antisense transcripts), most of whose functions are unknown. These RNAs (including those derived from introns) appear to comprise a hidden layer of internal signals that control various levels of gene expression in physiology and development, including chromatin architecture/epigenetic memory, transcription, RNA splicing, editing, translation and turnover. RNA regulatory networks may determine most of our complex characteristics, play a significant role in disease and constitute an unexplored world of genetic variation both within and between species.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                December 2020
                13 October 2020
                : 9
                : 12
                : 1202-1211
                Affiliations
                [1 ]Department of Endocrine and Metabolic Diseases , Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [2 ]Shanghai National Clinical Research Center for Metabolic Diseases , Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [3 ]Guangdong Geriatric Institute , Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
                [4 ]Reproductive Medicine Center , Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
                [5 ]Division of Endocrinology , Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
                Author notes
                Correspondence should be addressed to F Huang or S Wang: huanggua724@ 123456126.com or shuwang999@ 123456hotmail.com

                *(Q Yin and Z Jin contributed equally to this work)

                Article
                EC-20-0373
                10.1530/EC-20-0373
                7774754
                33112836
                6a78d00d-f844-4934-817d-6bd3da1e5578
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 29 September 2020
                : 13 October 2020
                Categories
                Research

                graves’ disease,cd4+ t cells,lncrna,expression profile

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