ArticleCancer research2009
Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- Trial
- Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Obesity, Dietary Fats, and Gastrointestinal Cancer Risk-Potential Mechanisms Relating to Lipid Metabolism and Inflammation.Metabolites · 2024Review
- Epigenetic Modulation of Inflammatory Pathways in Myometrial Stem Cells and Risk of Uterine Fibroids.International journal of molecular sciences · 2023Article
- Review
- Microsatellite Instability: From the Implementation of the Detection to a Prognostic and Predictive Role in Cancers.International journal of molecular sciences · 2022Review
- Obesity, inflammation, and cancer in dogs: Review and perspectives.Frontiers in veterinary science · 2022Review
- Single-cell genomic profile-based analysis of tissue differentiation in colorectal cancer.Science China. Life sciences · 2021Article
- Review
- The tumor microenvironment of colorectal cancer metastases: opportunities in cancer immunotherapy.Immunotherapy · 2020Review
- Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk.The Proceedings of the Nutrition Society · 2019Article
- Role of epigenetics in transformation of inflammation into colorectal cancer.World journal of gastroenterology · 2019Review
- Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond.Frontiers in immunology · 2019Review
- Shaping functional gut microbiota using dietary bioactives to reduce colon cancer risk.Seminars in cancer biology · 2017Review
- Mechanisms of DNA damage, repair, and mutagenesis.Environmental and molecular mutagenesis · 2017Review
- Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells.International journal of molecular sciences · 2016Review
- Genetic-and-Epigenetic Interspecies Networks for Cross-Talk Mechanisms in Human Macrophages and Dendritic Cells during MTB Infection.Frontiers in cellular and infection microbiology · 2016Article
- Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability.Journal of the National Cancer Institute · 2015Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Sporadic human mismatch repair (MMR)-deficient colorectal cancers account for approximately 12.5% of all cases of colorectal cancer. MMR-deficient colorectal cancers are classically characterized by right-sided location, multifocality, mucinous histology, and lymphocytic infiltration. However, tumors in germ-line MMR-deficient mouse models lack these histopathologic features. Mice lacking the heterotrimeric G protein alpha subunit Gialpha2 develop chronic colitis and multifocal, right-sided cancers with mucinous histopathology, similar to human MMR-deficient colorectal cancer. Young Gialpha2-/- colonic epithelium has normal MMR expression but selectively loses MLH1 and consequently PMS2 expression following inflammation. Gialpha2-/- cancers have microsatellite instability. Mlh1 is epigenetically silenced not by promoter hypermethylation but by decreased histone acetylation. Chronically inflamed Gialpha2-/- colonic mucosa contains patchy hypoxia, with increased crypt expression of the hypoxia markers DEC-1 and BNIP3. Chromatin immunoprecipitation identified increased binding of the transcriptional repressor DEC-1 to the proximal Mlh1 promoter in hypoxic YAMC cells and colitic Gialpha2-/- crypts. Treating Gialpha2-/- mice with the histone deacetylase inhibitor suberoylanilide hydroxamic acid significantly decreased colitis activity and rescued MLH1 expression in crypt epithelial cells, which was associated with increased acetyl histone H3 levels and decreased DEC-1 binding at the proximal Mlh1 promoter, consistent with a histone deacetylase-dependent mechanism. These data link chronic hypoxic inflammation, epigenetic MMR protein down-regulation, development of MMR-deficient colorectal cancer, and the firstmouse model of somatically acquired MMR-deficient colorectal cancer.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.