TET1 and TDG Suppress Inflammatory Response in Intestinal Tumorigenesis: Implications for Colorectal Tumors With the CpG Island Methylator Phenotype.
Animals
Humans
Mice
Adenocarcinoma
/ genetics
Adenoma
/ genetics
Carcinogenesis
/ genetics
Cell Transformation, Neoplastic
/ genetics
Colonic Neoplasms
/ genetics
Colorectal Neoplasms
/ genetics
CpG Islands
/ genetics
DNA Methylation
DNA-Binding Proteins
/ genetics
Epigenesis, Genetic
Mixed Function Oxygenases
/ genetics
Phenotype
Proto-Oncogene Proteins
/ genetics
CpG Island Methylator Phenotype
DNA Demethylation
DNA Methylation
Inflammatory Response
Interferon Response
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
21
01
2022
revised:
28
12
2022
accepted:
14
01
2023
pmc-release:
01
05
2024
medline:
25
4
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
Aberrant DNA methylation is frequent in colorectal cancer (CRC), but underlying mechanisms and pathologic consequences are poorly understood. We disrupted active DNA demethylation genes Tet1 and/or Tdg from Apc There were increased numbers of small intestinal adenomas in Apc Our findings reveal a novel epigenetic regulation, linked to the type of genomic instability, by which TET1/TDG-mediated DNA demethylation decreases methylation levels and inflammatory/interferon/immune responses. CIMP in CRC is triggered by an imbalance of methylating activities over demethylating activities. These mice represent a model of CIMP CRC.
Sections du résumé
BACKGROUND & AIMS
Aberrant DNA methylation is frequent in colorectal cancer (CRC), but underlying mechanisms and pathologic consequences are poorly understood.
METHODS
We disrupted active DNA demethylation genes Tet1 and/or Tdg from Apc
RESULTS
There were increased numbers of small intestinal adenomas in Apc
CONCLUSIONS
Our findings reveal a novel epigenetic regulation, linked to the type of genomic instability, by which TET1/TDG-mediated DNA demethylation decreases methylation levels and inflammatory/interferon/immune responses. CIMP in CRC is triggered by an imbalance of methylating activities over demethylating activities. These mice represent a model of CIMP CRC.
Identifiants
pubmed: 36764492
pii: S0016-5085(23)00112-9
doi: 10.1053/j.gastro.2023.01.039
pmc: PMC10586516
mid: NIHMS1932834
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Mixed Function Oxygenases
EC 1.-
Proto-Oncogene Proteins
0
TET1 protein, human
EC 1.-
TET1 protein, mouse
0
Tdg protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
921-936.e1Subventions
Organisme : NCI NIH HHS
ID : R21 CA191956
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM144131
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA078412
Pays : United States
Organisme : NCI NIH HHS
ID : R29 CA078412
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218133
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006927
Pays : United States
Informations de copyright
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.
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