Transcriptomic landscape of lncRNAs in inflammatory bowel disease.

Aashiq H Mirza,Stefan E Seemann,Claus Hb Berthelsen,Xiaoyong Pan,Flemming Pociot,Mogens Vilien,Jan Gorodkin,Klaus S Frederiksen

doi:10.1186/s13073-015-0162-2

Abstract

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

Highlights

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
CD and UC samples were divided based on inflammation status confirmed by macroscopic and microscopic evaluations and pro-inflammatory gene signatures into inflamed and non-inflamed categories
Expressed genes in inflamed Crohn’s disease and inflamed ulcerative colitis are enriched within inflammatory bowel disease loci Since most disease-associated susceptibility single-nucleotide polymorphism (SNP) map to the non-coding regions in the genome, we looked for the presence of known IBD-associated SNPs within the Gencode v.15 annotated long non-coding RNA (lncRNA)

Summary

Introduction

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. Inflammatory bowel diseases (IBDs) are idiopathic chronic relapsing inflammatory conditions of the gastrointestinal tract. Crohn’s disease (CD) and ulcerative colitis (UC) are two most common forms of the IBD. UC involves only the rectum and colon, and is characterized by superficial inflammation that is restricted to the mucosa and submucosa with the presence of cryptitis and crypt abscesses. Disease activity in both CD and UC is typically relapsing and remitting and both conditions are often difficult to diagnose

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