ArticleCarcinogenesis2010
The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer.
Article in Carcinogenesis, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- The role of EZH2 in overall survival of colorectal cancer: a meta-analysis.Scientific reports · 2017Pooled it
- Prognostic significance of EZH2 expression in patients with oesophageal cancer: a meta-analysis.Journal of cellular and molecular medicine · 2016Pooled it
- Identification of hub genes predicting sensitivity to neoadjuvant chemoradiation in locally advanced rectal cancer.Radiology and oncology · 2025Article
- Transforming Cancer Diagnostics: The Emergence of Liquid Biopsy and Epigenetic Markers.MedComm · 2025Review
- EZH2 expression in colorectal carcinoma: an evaluation of clinicopathological and prognostic value.Discover oncology · 2025Article
- Combined Effect of Conventional Chemotherapy with Epigenetic Modulators on Glioblastoma.Genes · 2025Article
- Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.International journal of molecular sciences · 2024Article
- Circadian clock protein Bmal1 accelerates acute myeloid leukemia by inhibiting ferroptosis through the EBF3/ALOX15 axis.Cancer science · 2023Article
- EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.BMC bioinformatics · 2023Article
- Integrated analysis reveals common DNA methylation patterns of alcohol-associated cancers: A pan-cancer analysis.Frontiers in genetics · 2023Article
- Enhancer of zeste homolog 2-mediated paired box 8 methylation promotes gastrointestinal stromal tumor progression through Wnt4 downregulation.Cancer gene therapy · 2021Article
- The interplay between DNA and histone methylation: molecular mechanisms and disease implications.EMBO reports · 2021Review
- Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer.Journal of gastrointestinal cancer · 2021Article
- Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications.Oncogene · 2021Review
- Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2.Cell death discovery · 2021Article
- Profile of Basal Cell Carcinoma Mutations and Copy Number Alterations - Focus on Gene-Associated Noncoding Variants.Frontiers in oncology · 2021Article
- Contribution of DNA methylation and EZH2 in SRBC down-regulation in gastric cancer.Molecular biology reports · 2020Article
- Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India.Cancer cell international · 2020Article
- GSK343 induces programmed cell death through the inhibition of EZH2 and FBP1 in osteosarcoma cells.Cancer biology & therapy · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In gastric cancer, a new epigenetic mechanism of tumour suppressor loss has been suggested where the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is responsible for loss of expression of RUNX3. This is consistent with EZH2 upregulation in multiple cancer types being associated with poor prognosis. We investigated whether EZH2 influences the expression of RUNX3 in colorectal cancer (CRC) and whether this is independent of methylation. We determined protein and messenger RNA (mRNA) levels of EZH2 and RUNX3 and assessed RUNX3 methylation with methylation-specific polymerase chain reaction using 72 human CRCs and 8 CRC cell lines. We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation. Despite higher levels of EZH2 and lower levels of RUNX3 in CRC specimens in general, no inverse correlation between EZH2 and RUNX3 in paired samples was found arguing against a major role for histone methylation in silencing RUNX3 in CRC. Conversely, downregulation of RUNX3 mRNA in the same tumours was associated with RUNX3 DNA methylation (P < 0.05). In cell lines, knockdown of EZH2 removed the repressive chromatin marks from RUNX3 but did not result in RUNX3 re-expression. However, it prevented the re-silencing of RUNX3 after the removal of demethylating agents. In conclusion, DNA methylation is primarily responsible for the transcriptional silencing of RUNX3 in CRC, but EZH2 and histone methylation are necessary for its methylation-dependent re-silencing after the removal of demethylating agents. These results would predict that inhibitors of EZH2 and histone methylation would enhance the effects of demethylating agents in cancer therapy.
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Registered trials
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