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      Transcriptomic landscape of lncRNAs in inflammatory bowel disease

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          Abstract

          Background

          Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD.

          Methods

          In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls = 12) using an expression microarray platform.

          Results

          In our study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively, while in cases of the non-inflamed CD and UC, we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment ( P-value <0.001, Pearson’s Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed their involvement in the immune response, pro-inflammatory cytokine activity and MHC protein complex.

          Conclusions

          The lncRNA expression profiling in both inflamed and non-inflamed CD and UC successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggest their potential as biomarkers in IBD.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13073-015-0162-2) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Inflammatory bowel disease.

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              Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.

              Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                mirza@sund.ku.dk
                clbb@novonordisk.com
                seemann@rth.dk
                panxy@rth.dk
                ksf@novonordisk.com
                mogens.vilien@regionh.dk
                gorodkin@rth.dk
                flemming.pociot.01@regionh.dk
                Journal
                Genome Med
                Genome Med
                Genome Medicine
                BioMed Central (London )
                1756-994X
                13 May 2015
                13 May 2015
                2015
                : 7
                : 1
                : 39
                Affiliations
                [ ]Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, 1870 Denmark
                [ ]Department of Pediatrics E, Copenhagen Diabetes Research Center (CPH-DIRECT), Herlev University Hospital, Herlev, 2730 Denmark
                [ ]Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200 Denmark
                [ ]Department of Surgery, North Zealand Hospital, Hillerød, 3400 Denmark
                [ ]The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, 2200 Denmark
                [ ]Department of Obesity Biology, Novo Nordisk, Måløv, 2760 Denmark
                [ ]Department of Molecular Genetics, Novo Nordisk, Måløv, 2760 Denmark
                Article
                162
                10.1186/s13073-015-0162-2
                4437449
                25991924
                3864025b-43e4-45f9-bce2-9ba2064c32bd
                © Mirza et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 November 2014
                : 9 April 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Molecular medicine
                Molecular medicine

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