ArticleEpigenetics2010
Ischemia dysregulates DNA methyltransferases and p16INK4a methylation in human colorectal cancer cells.
Article in Epigenetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Meta-Analysis of the Prognostic and Predictive Role of the CpG Island Methylator Phenotype in Colorectal Cancer.Disease markers · 2022Pooled it
- Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors.The Journal of nutrition · 2015Trial
- Time-dependent memory of hypoxia exposure influences tumor invasion dynamics.bioRxiv : the preprint server for biology · 2026Article
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Comparison of hypoxia- and hyperoxia-induced alteration of epigene expression pattern in lungs of Pleurodeles waltl and Mus musculus.PloS one · 2024Article
- Physoxia Influences Global and Gene-Specific Methylation in Pluripotent Stem Cells.International journal of molecular sciences · 2022Article
- Role of epigenetics in cellular reprogramming; from iPSCs to disease modeling and cell therapy.Journal of cellular biochemistry · 2022Review
- Epigenetic Regulation During Hypoxia and Its Implications in Cancer.Sub-cellular biochemistry · 2022Article
- Telomerase Regulation: A Role for Epigenetics.Cancers · 2021Review
- TET is targeted for proteasomal degradation by the PHD-pVHL pathway to reduce DNA hydroxymethylation.The Journal of biological chemistry · 2020Article
- Hypoxic Regulation of Gene Transcription and Chromatin: Cause and Effect.International journal of molecular sciences · 2020Review
- The failure of DAC to induce OCT2 expression and its remission by hemoglobin-based nanocarriers under hypoxia in renal cell carcinoma.Theranostics · 2020Article
- Review
- Review
- Interplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches.Oncogene · 2017Review
- Epigenetics, TET proteins, and hypoxia in epithelial-mesenchymal transition and tumorigenesis.BioMedicine · 2016Article
- Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes.Journal of clinical medicine · 2016Review
- EMODIN EFFICACY ON THE AKT, MAPK, ERK AND DNMT EXPRESSION PATTERN DURING DMBA-INDUCED ORAL CARCINOMA IN GOLDEN SYRIAN HAMSTERS.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2016Article
- Review
- HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth.Cell reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic modifications are involved in the initiation and progression of cancer. Expression patterns and activity of DNA methyltransferases (DNMTs) are strictly controlled in normal cells, however, regulation of these enzymes is lost in cancer cells due to unknown reasons. Cancer therapies which target DNMTs are promising treatments of hematologic cancers, but they lack effectiveness in solid tumors. Solid tumors exhibit areas of hypoxia and hypoglycaemia due to their irregular and dysfunctional vasculature, and we previously showed that hypoxia reduces global DNA methylation. Colorectal carcinoma (CRC) cells (HCT116 and 379.2; p53+/+ and p53-/-, respectively) were subjected to ischemia (hypoxia and hypoglycaemia) in vitro, and levels of DNMTs were assessed. We found a significant decrease in mRNA for DNMT1, DNMT3a and DNMT3b, and similar reductions in DNMT1 and DNMT3a protein levels were detected by western blotting. In addition, total activity levels of DNMTs (as measured by an ELISA-based DNMT activity assay) were reduced in cells exposed to hypoxic and hypoglycaemic conditions. Immunofluorescence of HCT116 tumor xenografts demonstrated an inverse relationship between ischemia (as revealed by carbonic anhydrase IX staining) and DNMT1 protein. Bisulfite sequencing of the proximal promoter region of p16INK4a showed a decrease in 5-methylcytosine following in vitro exposure to ischemia. These studies provide evidence for the down-regulation of DNMTs and modulation of methylation patterns by hypoxia and hypoglycaemia in human CRC cells, both in vitro and in vivo. Our findings suggest that ischemia, either intrinsic or induced through the use of anti-angiogenic drugs, may influence epigenetic patterning and hence tumor progression.
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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.