ArticleCancer research2016
Histone H3K27 Trimethylation Modulates 5-Fluorouracil Resistance by Inhibiting PU.1 Binding to the DPYD Promoter.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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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
17 citing papers in PubMed, 24 citations in OpenAlex.
- Enhancer-mediated DDIT4 activation by SMYD2-dependent H3K4me1 promotes pazopanib resistance in clear cell renal cell carcinoma.Journal of translational medicine · 2026Article
- Unlocking the Epigenetic Landscape of Colorectal Cancer: A Step Toward Epigenetics to Precision.Sub-cellular biochemistry · 2026Review
- Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.Journal of advanced research · 2025Article
- Glucagon Enhances Chemotherapy Efficacy By Inhibition of Tumor Vessels in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Fluoropyrimidine Toxicity: the Hidden Secrets of DPYD.Current drug metabolism · 2024Review
- Long noncoding RNA SNHG6 silencing sensitized esophageal cancer cells to 5-FU via EZH2/STAT pathway.Scientific reports · 2023Article
- Pharmacogenomic-guided dosing of fluoropyrimidines beyondFrontiers in pharmacology · 2023Review
- Review
- Epigenetic Regulation Towards Acquired Drug Resistance in Cancer.Sub-cellular biochemistry · 2022Article
- Hypoxia Drives Dihydropyrimidine Dehydrogenase Expression in Macrophages and Confers Chemoresistance in Colorectal Cancer.Cancer research · 2021Article
- DPYD, down-regulated by the potentially chemopreventive agent luteolin, interacts with STAT3 in pancreatic cancer.Carcinogenesis · 2021Article
- Increased S1P induces S1PR2 internalization to blunt the sensitivity of colorectal cancer to 5-fluorouracil via promoting intracellular uracil generation.Acta pharmacologica Sinica · 2021Article
- Article
- Dynamic control of the T-cell specification gene regulatory network.Current opinion in systems biology · 2019Article
- EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression.OncoTargets and therapy · 2019Article
- EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression.OncoTargets and therapy · 2018Article
- Quantitative Contribution of rs75017182 to Dihydropyrimidine Dehydrogenase mRNA Splicing and Enzyme Activity.Clinical pharmacology and therapeutics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The antimetabolite 5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs. Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU response and toxicity. Although DPYD variants may affect 5-FU metabolism, they do not completely explain the reported variability in DPD function or the resultant differences in treatment response. Here, we report that H3K27 trimethylation (H3K27me3) at the DPYD promoter regulated by Ezh2 and UTX suppresses DPYD expression by inhibiting transcription factor PU.1 binding, leading to increased resistance to 5-FU. Enrichment of H3K27me3 at the DPYD promoter was negatively correlated with both DPYD expression and DPD enzyme activity in peripheral blood specimens from healthy volunteers. Lastly, tumor expression data suggest that DPYD repression by Ezh2 predicts poor survival in 5-FU-treated cancers. Collectively, the findings of the present article suggest that a previously uncharacterized mechanism regulates DPD expression and may contribute to tumor resistance to 5-FU. Cancer Res; 76(21); 6362-73. ©2016 AACR.
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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.