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Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease
Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogene...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513375/ https://www.ncbi.nlm.nih.gov/pubmed/36177008 http://dx.doi.org/10.3389/fimmu.2022.991346 |
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author | Boros, Éva Hegedűs, Zoltán Kellermayer, Zoltán Balogh, Péter Nagy, István |
author_facet | Boros, Éva Hegedűs, Zoltán Kellermayer, Zoltán Balogh, Péter Nagy, István |
author_sort | Boros, Éva |
collection | PubMed |
description | Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogenesis. Understanding the molecular mechanisms such as alterations in microRNAome upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of IBD. Hence, we conducted a genome wide microRNAome analysis by applying miRNA-Seq in a rat model of experimental colitis, validated the data by QPCR, examined the expression of a selection of precursor and mature miRNAs, performed in depth biological interpretation using Ingenuity Pathway Analysis and tested the obtained results on samples derived from human patients. We identified specific, interdependent expression pattern of activator/repressor transcription factors, miRNAs and their direct targets in the inflamed colon samples. Particularly, decreased expression of the miR-200 family members (miR-200a/b/c,-141, and -429) and miR-27b correlates with the reduced level of their enhancers (HNF1B, E2F1), elevated expression of their repressors (ZEB2, NFKB1) and increased expression of their target genes (ZEB2, RUNX1). Moreover, the marked upregulation of six miR-27b target genes (IFI16, GCA, CYP1B1, RUNX1, MEF2C and MMP13) in the inflamed colon tissues is a possible direct consequence of the lack of repression due to the downregulated miRNA-27b expression. Our data indicate that changes in microRNAome are associated with the pathophysiology of IBD, consequently, microRNAs offer potential targets for the diagnosis, prognosis and treatment of IBD. |
format | Online Article Text |
id | pubmed-9513375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95133752022-09-28 Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease Boros, Éva Hegedűs, Zoltán Kellermayer, Zoltán Balogh, Péter Nagy, István Front Immunol Immunology Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogenesis. Understanding the molecular mechanisms such as alterations in microRNAome upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of IBD. Hence, we conducted a genome wide microRNAome analysis by applying miRNA-Seq in a rat model of experimental colitis, validated the data by QPCR, examined the expression of a selection of precursor and mature miRNAs, performed in depth biological interpretation using Ingenuity Pathway Analysis and tested the obtained results on samples derived from human patients. We identified specific, interdependent expression pattern of activator/repressor transcription factors, miRNAs and their direct targets in the inflamed colon samples. Particularly, decreased expression of the miR-200 family members (miR-200a/b/c,-141, and -429) and miR-27b correlates with the reduced level of their enhancers (HNF1B, E2F1), elevated expression of their repressors (ZEB2, NFKB1) and increased expression of their target genes (ZEB2, RUNX1). Moreover, the marked upregulation of six miR-27b target genes (IFI16, GCA, CYP1B1, RUNX1, MEF2C and MMP13) in the inflamed colon tissues is a possible direct consequence of the lack of repression due to the downregulated miRNA-27b expression. Our data indicate that changes in microRNAome are associated with the pathophysiology of IBD, consequently, microRNAs offer potential targets for the diagnosis, prognosis and treatment of IBD. Frontiers Media S.A. 2022-09-13 /pmc/articles/PMC9513375/ /pubmed/36177008 http://dx.doi.org/10.3389/fimmu.2022.991346 Text en Copyright © 2022 Boros, Hegedűs, Kellermayer, Balogh and Nagy https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Boros, Éva Hegedűs, Zoltán Kellermayer, Zoltán Balogh, Péter Nagy, István Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title | Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title_full | Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title_fullStr | Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title_full_unstemmed | Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title_short | Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease |
title_sort | global alteration of colonic micrornaome landscape associated with inflammatory bowel disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513375/ https://www.ncbi.nlm.nih.gov/pubmed/36177008 http://dx.doi.org/10.3389/fimmu.2022.991346 |
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