Dataset Information

Genome-wide DNA Methylation in Treatment-naive Ulcerative Colitis.

ABSTRACT: Background and Aims:The aim of this study was to investigate the genome-wide DNA methylation status in treatment-naïve ulcerative colitis [UC], and to explore the relationship between DNA methylation patterns and gene expression levels in tissue biopsies from a well-stratified treatment-naïve UC patient group. Methods:Mucosal biopsies from treatment-naïve patients [n = 10], and a healthy control group [n = 11] underwent genome-wide DNA bisulfite sequencing. Principal component analysis [PCA] and diverse statistical methods were applied to obtain a dataset of differentially methylated genes. DNA methylation annotation was investigated using the UCSC Genome Browser. Gene set enrichments were obtained using the Kyoto Encyclopaedia of Genes and Genomes [KEGG] and PANTHER. Results:Of all significantly differentially expressed genes [DEGs], 25% correlated with DNA methylation patterns; 30% of these genes were methylated at CpG sites near their transcription start site [TSS]. Hyper-methylation was observed for genes involved in homeostasis and defence, whereas hypo-methylation was observed for genes playing a role in immune response [i.e. chemokines and interleukins]. Of the differentially DNA methylated genes, 25 were identified as inflammatory bowel disease [IBD] susceptibility genes. Four genes [DEFFA6, REG1B, BTNL3, OLFM4] showed DNA methylation in the absence of known CpG islands. Conclusions:Genome-wide DNA methylation analysis revealed distinctive functional patterns for hyper-and hypo-methylation in treatment-naïve UC. These distinct patterns could be of importance in the development and pathogenesis of UC. Further investigation of DNA methylation patterns may be useful in the development of the targeting of epigenetic processes, and may allow new treatment and target strategies for UC patients.

SUBMITTER: Taman H

PROVIDER: S-EPMC6236200 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Genome-wide DNA Methylation in Treatment-naïve Ulcerative Colitis.

Taman Hagar H Fenton Christopher G CG Hensel Inga V IV Anderssen Endre E Florholmen Jon J Paulssen Ruth H RH

Journal of Crohn's & colitis 20181101 11

<h4>Background and aims</h4>The aim of this study was to investigate the genome-wide DNA methylation status in treatment-naïve ulcerative colitis [UC], and to explore the relationship between DNA methylation patterns and gene expression levels in tissue biopsies from a well-stratified treatment-naïve UC patient group.<h4>Methods</h4>Mucosal biopsies from treatment-naïve patients [n = 10], and a healthy control group [n = 11] underwent genome-wide DNA bisulfite sequencing. Principal component ana ...[more]

PMID: 30137272

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Project description:Inflammatory Bowel Disease--comprised of Crohn's Disease and Ulcerative Colitis (UC)--is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals. Through Significance Analysis of Microarrays, a signature of 31 differentially expressed platelet-derived miRNAs has been identified and biomarker performance estimated through a non-probabilistic binary linear classification using Support Vector Machines. Through this approach, classifier measurements reveal a predictive score of 92.8% accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients from normal individuals. Additionally, the platelet-derived biomarker signature can be validated at 88% accuracy through qPCR assays, and a majority of the miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated intensity based clusters. Analysis of predicted targets of these biomarkers reveal an enrichment of pathways associated with cytoskeleton assembly, transport, membrane permeability and regulation of transcription factors engaged in a variety of regulatory cascades that are consistent with a cell-mediated immune response model of intestinal inflammation. Interestingly, comparison of the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide association studies identifies a physical linkage between hsa-miR-941 and a UC susceptibility loci located on Chr 20. Taken together, analysis of these expression maps outlines a promising catalog of novel platelet-derived miRNA biomarkers of clinical utility and provides insight into the potential biological function of these candidates in disease pathogenesis.

Project description:Acupuncture and moxibustion have definite clinical effects on treating ulcerative colitis (UC), but their mechanism is still unclear. To investigate the molecular mechanisms, we applied herb-partitioned moxibustion or electroacupuncture at the Tianshu (ST25) points on UC rats and used RNA sequencing to identify molecular consequences. Male Sprague Dawley (SD) rats were divided into 6 groups randomly: the normal control (NC) group, the control + herb-partitioned moxibustion (NCHM) group, the control + electroacupuncture (NCEA) group, the model (UC) group, the model + herb-partitioned moxibustion (UCHM) group, and the model + electroacupuncture (UCEA) group. Compared to the UC group, HE staining in the UCHM group and UCEA group indicated that colitis was relieved, the histopathological score and MPO were both significantly reduced, and the serum hs-CRP concentration was decreased significantly. The results of RNA-seq suggested that, compared to the NC group, 206 upregulated genes and 167 downregulated genes were identified in colon tissues from the UC group; compared to the UC group, the expression levels of some genes were both affected in the UCHM group and the UCEA group (684 differentially expressed genes were identified in the UCHM group, and 1182 differentially expressed genes were identified in the UCEA group). KEGG signal pathway analysis indicated that the differentially expressed genes in the UCHM group were associated with the JAK-STAT signaling pathway and cell adhesion molecule (CAM); the differentially expressed genes in the UCEA group were associated with the NF-κB signaling pathway, the toll-like receptor signaling pathways, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Wnt signaling pathway. This is the first study to reveal the gene expression characteristics of the anti-inflammatory effect of UC rats from the perspective of acupuncture and moxibustion control, which provide a clue for further investigation into the molecular mechanisms of UC treatment by acupuncture and moxibustion.

Dataset Information

Genome-wide DNA Methylation in Treatment-naive Ulcerative Colitis.

Publications

Genome-wide DNA Methylation in Treatment-naïve Ulcerative Colitis.

Similar Datasets

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