Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Boros, Éva, Hegedűs, Zoltán, Kellermayer, Zoltán, Balogh, Péter, Nagy, István
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784798048352731136
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
work_keys_str_mv AT boroseva globalalterationofcolonicmicrornaomelandscapeassociatedwithinflammatoryboweldisease
AT hegeduszoltan globalalterationofcolonicmicrornaomelandscapeassociatedwithinflammatoryboweldisease
AT kellermayerzoltan globalalterationofcolonicmicrornaomelandscapeassociatedwithinflammatoryboweldisease
AT baloghpeter globalalterationofcolonicmicrornaomelandscapeassociatedwithinflammatoryboweldisease
AT nagyistvan globalalterationofcolonicmicrornaomelandscapeassociatedwithinflammatoryboweldisease