scholarly journals Epigenetic Regulation of Glycosylation in Cancer and Other Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 2980
Author(s):  
Rossella Indellicato ◽  
Marco Trinchera
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
Transcription Factors ◽  
Epigenetic Regulation ◽  
Bowel Disease ◽  
Noncoding Rnas ◽  
Fine Tuning ◽  
Epigenetic Mechanisms ◽  
Complex Process ◽  
Inflammatory Bowel

In the last few decades, the newly emerging field of epigenetic regulation of glycosylation acquired more importance because it is unraveling physiological and pathological mechanisms related to glycan functions. Glycosylation is a complex process in which proteins and lipids are modified by the attachment of monosaccharides. The main actors in this kind of modification are the glycoenzymes, which are translated from glycosylation-related genes (or glycogenes). The expression of glycogenes is regulated by transcription factors and epigenetic mechanisms (mainly DNA methylation, histone acetylation and noncoding RNAs). This review focuses only on these last ones, in relation to cancer and other diseases, such as inflammatory bowel disease and IgA1 nephropathy. In fact, it is clear that a deeper knowledge in the fine-tuning of glycogenes is essential for acquiring new insights in the glycan field, especially if this could be useful for finding novel and personalized therapeutics.

scholarly journals Network Analysis of Inflammatory Bowel Disease Reveals PTPN2 As New Monogenic Cause of Intestinal Inflammation

2019 ◽  
Author(s):  
Marianna Parlato ◽  
Julia Pazmandi ◽  
Qing Nian ◽  
Fabienne Charbit-Henrion ◽  
Bernadette Bègue ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Random Walk ◽  
Bowel Disease ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Genome Wide Association Studies ◽  
Causal Genes ◽  
Disease Module ◽  
Inflammatory Bowel ◽  
Stat Pathway

ABSTRACTBACKGROUND & AIMSGenome-wide association studies (GWAS) have uncovered multiple loci associated with inflammatory bowel disease (IBD), yet delineating functional consequences is complex. We used a network-based approach to uncover traits common to monogenic and polygenic forms of IBD in order to reconstruct disease relevant pathways and prioritize causal genes.METHODSWe have used an iterative random walk with restart to explore network neighborhood around the core monogenic IBD cluster and disease-module cohesion to identify functionally relevant GWAS genes. Whole exome sequencing was used to screen a cohort of monogenic IBD for germline mutations in top GWAS genes. One mutation was identified and validated by a combination of biochemical approaches.RESULTSMonogenic IBD genes clustered siginificantly on the molecular networks and had central roles in network topology. Iterative random walk from these genes allowed to rank the GWAS genes, among which 14 had high disease-module cohesion and were selected as putative causal genes. As a proof of concept, a germline loss of function mutation was identified in PTPN2, one of the top candidates, as a novel genetic etiology of early-onset intestinal autoimmunity. The mutation abolished the catalytic activity of the enzyme, resulting in haploinsufficiency and hyper-activation of the JAK/STAT pathway in lymphocytes.CONCLUSIONSOur network-based approach bridges the gap between large-scale network medicine prediction and single-gene defects and underscores the crucial need of fine tuning the JAK/STAT pathway to preserve intestinal immune homeostasis. Our data provide genetic-based rationale for using drugs targeting the JAK/STAT pathway in IBD.

Epigenetic Modifications of the Nuclear Factor Kappa B Signalling Pathway and its Impact on Inflammatory Bowel Disease

2021 ◽  
Vol 27 ◽  
Author(s):  
Stamatia Papoutsopoulou ◽  
Barry J. Campbell
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Nuclear Factor Kappa B ◽  
Intestinal Inflammation ◽  
Alternative Pathway ◽  
Current Evidence ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Inflammatory Bowel

Background: Inflammatory bowel disease (IBD) is a multifactorial condition influenced by the immune system, the intestinal microbiota, environmental factors, genetic and epigenetic factors. Genetic- and environment-induced dysregulation of the Nuclear Factor-kappa B (NF-κB) transcription factor pathway has been linked to IBD pathogenesis. Objective: To assess the current evidence in relation to the contribution of the classical and alternative NF-κB pathways in IBD and to discuss the epigenetic mechanisms that impact on NF-κB function. Methods: A Medline search for ‘NF-kappaB/NF-κB’, in combination with terms including ‘inflammatory bowel disease/IBD’, 'intestinal inflammation', ‘Crohn's disease’, ‘ulcerative colitis’, 'colitis'; ‘epigenetics’, ‘DNA methylation’, ‘histones’, ‘microRNAs/miRNAs’ and ‘short non-coding/long non-coding RNAs’ was performed. Results: Both NF-κB pathways contribute to the chronic inflammation underlying IBD by regulating the inflammatory immune responses and homeostasis of the intestinal epithelium (classical pathway) or regulating bowel inflammation and epithelial microfold (M) cell function (alternative pathway). DNA methylation is a common epigenetic modification in intestinal inflammation, including NFKB1 and RELA loci. Conversely, little is understood regarding epigenetic effects on genes encoding other NF-κB subunits, particularly those of the alternative pathway, and in the context of IBD. However, NF-κB interaction with chromatin modifiers is also seen to be an essential mechanism of regulation of downstream target genes relevant to NF-κB-mediated inflammatory responses. Conclusion: Further research is clearly warranted in this area, as understanding the cell-specific regulation of the NF-κB pathways will bring researchers into a position to achieve more efficient stratification of IBD patients, and more targeted and effective choice of treatment.

scholarly journals DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis

2015 ◽  
Vol 10 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Edel McDermott ◽  
Elizabeth J. Ryan ◽  
Miriam Tosetto ◽  
David Gibson ◽  
Joe Burrage ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Pathogenesis ◽  
Dna Methylation Profiling ◽  
Inflammatory Bowel ◽  
Methylation Profiling

scholarly journals The Emerging Role of Noncoding RNAs in Pediatric Inflammatory Bowel Disease

2020 ◽  
Vol 26 (7) ◽  
pp. 985-993 ◽  
Author(s):  
Petr Jabandziev ◽  
Julia Bohosova ◽  
Tereza Pinkasova ◽  
Lumir Kunovsky ◽  
Ondrej Slaby ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Noncoding Rnas ◽  
Inflammatory Disorder ◽  
Altered Expression ◽  
Clinical Biomarkers ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years—not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.

OC-010 Epigenome-wide dna methylation profiling in inflammatory bowel disease

Gut ◽  
2015 ◽  
Vol 64 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
NT Ventham ◽  
NA Kennedy ◽  
AT Adams ◽  
R Kalla ◽  
KR O’Leary ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Dna Methylation Profiling ◽  
Inflammatory Bowel ◽  
Methylation Profiling

W1235 Inflammatory Bowel Disease (IBD)-Associated DNA Methylation in B Cells From IBD Patients

2010 ◽  
Vol 138 (5) ◽  
pp. S-680
Author(s):  
Zhenwu Lin ◽  
John P. Hegarty ◽  
Wei Yu ◽  
Jonathan A. Cappel ◽  
Xi Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
B Cells ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?

2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Lihui Lin ◽  
Gaoshi Zhou ◽  
Peng Chen ◽  
Ying Wang ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Inflammatory Bowel
Sign in / Sign up

Export Citation Format

Share Document