Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Xu, Lili; Ma, Lili; Lian, Jie; Yang, Jingchun; Chen, Shiyao

doi:10.3892/mmr.2016.4880

Cited by 8 publications

(8 citation statements)

References 30 publications

(32 reference statements)

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“…Various transcriptomic studies have been carried out in the IBD field, including several efforts to discriminate between disease subtypes [Crohn’s disease vs UC], disease phase [active/mildly active/inactive], 7,8 colon biopsy locations, 9 genders, 10 etc. Some of these studies have also been previously reviewed.…”

Section: Introductionmentioning

confidence: 99%

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Low

Mokhtar

Wong

et al. 2019

Journal of Crohn's and Colitis

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Background and aims Patients with ulcerative colitis [UC] with long disease duration have a higher risk of developing colitis-associated cancer [CAC] compared with patients with short-duration UC. The aim of this study was to identify transcriptomic differences associated with the duration of UC disease. Methods We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR. Results There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2 , MEP1B , GUCA2B , ADH1C , OTOP2 , SLC9A3 , and LYPD8 ; the top ten downregulated genes were PI3 , DUOX2 , VNN1 , SLC6A14 , GREM1 , MMP1 , CXCL1 , TNIP3 , TFF1 , and LCN2 . Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator–activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing. Conclusions Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.

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Section: Introductionmentioning

confidence: 99%

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Low

Mokhtar

Wong

et al. 2019

Journal of Crohn's and Colitis

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“… 17 34 35 In transcriptomic studies of IBD, most of the aberrant mRNAs were found to be involved in molecular functions associated with immune response, mucosal inflammation, nutrients absorption, epithelial damage, oncogenesis and cell proliferation. 21 36 37 …”

Section: Different Types Of Rnas and Their Associations With Diseasesmentioning

confidence: 99%

Delineating inflammatory bowel disease through transcriptomic studies: current review of progress and evidence

et al. 2018

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Inflammatory bowel disease (IBD), which comprises of Crohn's disease and ulcerative colitis, is an idiopathic relapsing and remitting disease in which the interplay of different environment, microbial, immunological and genetic factors that attribute to the progression of the disease. Numerous studies have been conducted in multiple aspects including clinical, endoscopy and histopathology for the diagnostics and treatment of IBD. However, the molecular mechanism underlying the aetiology and pathogenesis of IBD is still poorly understood. This review tries to critically assess the scientific evidence at the transcriptomic level as it would help in the discovery of RNA molecules in tissues or serum between the healthy and diseased or different IBD subtypes. These molecular signatures could potentially serve as a reliable diagnostic or prognostic biomarker. Researchers have also embarked on the study of transcriptome to be utilized in targeted therapy. We focus on the evaluation and discussion related to the publications reporting the different approaches and techniques used in investigating the transcriptomic changes in IBD with the intention to offer new perspectives to the landscape of the disease.

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“…They discovered that several genes were deregulated in the inactive UC despite histological recovery [ 5 ]. Another microarray study demonstrated that expression of INF‑γ and IL‑17 was comparably elevated in both inflamed and unaffected colon mucosa from patients with IBD, indicating that the inflammatory response is not limited to the endoscopic lesions [ 6 ]. Smith et al identified that dysregulation of BMP/retinoic acid inducible neural specific 3 plays a role in the pathogenesis of UC [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of alternative splicing is associated with the pathogenesis of ulcerative colitis

Tan

2021

BioMed Eng OnLine

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Background Although numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Recently, multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study also demonstrated that altered post-transcriptional regulation is involved in the progression of UC. Here, we provide a genome-wide analysis of alternative splicing (AS) signatures in UC patients. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events. Results Skipped exon and alternative first exon were the two most significantly altered AS events in UC patients. The immune response-related pathways were remarkably enriched in the UC-related AS events. Genes with significant AS events were more likely to be dysregulated at the expression level. Conclusions We present a genomic landscape of AS events in UC patients based on a combined analysis of two cohorts. Our results indicate that dysregulation of AS may have a pivotal role in determining the pathogenesis of UC. In addition, our study uncovers genes with potential therapeutic implications for UC treatment.

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Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Cited by 8 publications

References 30 publications

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Delineating inflammatory bowel disease through transcriptomic studies: current review of progress and evidence

Dysregulation of alternative splicing is associated with the pathogenesis of ulcerative colitis

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