ArticleJournal of molecular cell biology2020
Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin.
Article in Journal of molecular cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
- Co-Occurrence of Nuclear-Catenin and H3K27me3 Expression in Advanced Colorectal Cancer: A Retrospective Observational Study.Current oncology (Toronto, Ont.) · 2026Observational
- Unlocking the Epigenetic Landscape of Colorectal Cancer: A Step Toward Epigenetics to Precision.Sub-cellular biochemistry · 2026Review
- Expression of ubiquitin carboxyl-terminal hydrolase isozyme L1 and chromogranin A regulated via histone-modification through Rho/ERK/NFκB signaling in oxaliplatin-resistant colorectal cancer cells.International journal of medical sciences · 2026Article
- Anti-tumor effects and mechanism of the histone demethylase inhibitor GSK-J4 in non-small cell lung cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.Clinical epigenetics · 2025Review
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- The clinical and molecular landscape of breast cancer in women of African and South Asian ancestry.Nature communications · 2025Article
- [High expression of DTX2 promotes proliferation, invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Demystifying the Role of Histone Demethylases in Colorectal Cancer: Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2025Review
- Prognostic value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant.Journal of neuro-oncology · 2025Article
- Lentinan inhibits colorectal cancer stemness by binding CD133 and suppressing the CD133/p85/p-AKT signaling axis.Frontiers in pharmacology · 2025Article
- Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B.Cell communication and signaling : CCS · 2024Article
- The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma.Histology and histopathology · 2024Article
- Epigenetics in thyroid cancer: a bibliometric analysis.Endocrine connections · 2024Article
- The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer.Stem cells (Dayton, Ohio) · 2024Review
- Inactivation of KDM6A promotes the progression of colorectal cancer by enhancing the glycolysis.European journal of medical research · 2024Article
- Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer.Clinical epigenetics · 2024Article
- The Intersection of Epigenetic Alterations and Developmental State in Pediatric Ependymomas.Developmental neuroscience · 2024Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone methylation is a context-dependent modification that regulates gene expression, and the trimethylation of histone H3 lysine 27 (H3K27me3) usually induces gene silencing. Overcoming colorectal cancer (CRC) chemoresistance is currently a huge challenge, but the relationship between H3K27me3 modification and chemoresistance remains largely unclear. Here, we found that H3K27me3 levels positively correlated with the metastasis-free survival of CRC patients and a low H3K27me3 level predicted a poor outcome upon chemotherapeutic drug treatment. Oxaliplatin stimulation significantly induced the expression of H3K27 lysine demethylase 6A/6B (KDM6A/6B), thus decreasing the level of H3K27me3 in CRC cells. Elevation of H3K27me3 level through KDM6A/6B depletion or GSK-J4 (a KDM6A/6B inhibitor) treatment significantly enhanced oxaliplatin-induced apoptosis. Conversely, when inhibiting the expression of H3K27me3 by EPZ-6438, an inhibitor of the histone methyltransferase EZH2, the proportion of apoptotic cells remarkably decreased. In addition, the combination of GSK-J4 and oxaliplatin significantly inhibited tumor growth in an oxaliplatin-resistant patient-derived xenograft model. Importantly, we revealed that oxaliplatin treatment dramatically induced NOTCH2 expression, which was caused by downregulation of H3K27me3 level on the NOTCH2 transcription initiation site. Thus, the activated NOTCH signaling promoted the expression of stemness-related genes, which resulted in oxaliplatin resistance. Furthermore, oxaliplatin-induced NOTCH signaling could be interrupted by GSK-J4 treatment. Collectively, our findings suggest that elevating H3K27me3 level can improve drug sensitivity in CRC patients.
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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.