ArticleCancer science2024
EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.
Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 25 citations in OpenAlex.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- Epigenetic regulation of NDGA and its synergistic inhibition with EZH2 inhibitors in prostate cancer via NRP1.Acta pharmacologica Sinica · 2026Article
- Crosstalk BetweenCancers · 2026Review
- TheJournal of gastrointestinal oncology · 2026Article
- AP-2 Transcription Factors as Regulators of Ferroptosis: A Family-Wide Profiling in Diverse Cancer Contexts.International journal of molecular sciences · 2026Article
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- The Landscape of Ferroptosis-Related Gene Signatures as Molecular Stratification in Triple-Negative Breast Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities.Cell death & disease · 2025Review
- Co-targeting ferroptosis and immune evasion through small molecules in breast cancer.Journal of translational internal medicine · 2025Article
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- HSPB1/KDM1 A facilitates ANXA2 expression via hypomethylated DNA promoter to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Review
- ATOH8 confers the vulnerability of tumor cells to ferroptosis by repressing SCD expression.Cell death and differentiation · 2025Article
- Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).International journal of molecular medicine · 2025Review
- Bioinformatics-Based Analysis of Ferroptosis-Related Biomarkers and the Prediction of Drugs Affecting the Adipogenic Differentiation of MSCs.Biomedicines · 2025Article
- Radiomics and molecular analysis: Bridging the gap for predicting hepatocellular carcinoma prognosis.World journal of clinical cases · 2025Article
- Key oncogenes and candidate drugs for hepatitis-B-driven hepatocellular carcinoma progression.Discover oncology · 2025Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.
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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.