ArticleTranslational oncology2020
Inhibition of EZH2 Attenuates Sorafenib Resistance by Targeting NOTCH1 Activation-Dependent Liver Cancer Stem Cells via NOTCH1-Related MicroRNAs in Hepatocellular Carcinoma.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- Immunotherapy targeting liver cancer tumor-initiating cells: challenges, mechanisms, and emerging therapeutic horizons.Frontiers in immunology · 2025Review
- Targeting Hepatic Cancer Stem Cells (CSCs) and Related Drug Resistance by Small Interfering RNA (siRNA).Cell biochemistry and biophysics · 2024Review
- Identification of ETV5 as a prognostic marker related to epigenetic modification in pan-cancer and facilitates tumor progression in hepatocellular carcinoma.Scientific reports · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death.BMC complementary medicine and therapies · 2023Article
- SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.iScience · 2023Article
- Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC.Biomedicines · 2023Article
- Four-gene signature predicting overall survival and immune infiltration in hepatocellular carcinoma by bioinformatics analysis with RT‒qPCR validation.BMC cancer · 2022Article
- Clinicopathological Analysis of Expression of Enhancer of Zeste Homologue 2 in Canine Mammary Carcinoma.Journal of veterinary research · 2022Article
- Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Advances in Liver Cancer Stem Cell Isolation and their Characterization.Stem cell reviews and reports · 2021Review
- miRNA signaling networks in cancer stem cells.Regenerative therapy · 2021Article
- miR‑34c‑5p targets Notch1 and suppresses the metastasis and invasion of cervical cancer.Molecular medicine reports · 2021Article
- Inhibition of RFX6 Suppresses the Invasive Ability of Tumor Cells Through the Notch Pathway and Affects Tumor Immunity in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Single-Cell RNA Sequencing Reveals the Role of Phosphorylation-Related Genes in Hepatocellular Carcinoma Stem Cells.Frontiers in cell and developmental biology · 2021Article
- The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance and intrinsic to sorafenib therapy represents a major hurdle in improving the management of advanced hepatocellular carcinoma (HCC), which has been recently shown to be associated with the emergence of liver cancer stem cells (CSCs). However, it remains largely unknown whether and how histone posttranslational modifications, especially H3K27me3, are causally linked to the maintenance of self-renewal ability in sorafenib-resistant HCC. Here, we found that NOTCH1 signaling was activated in sorafenib-resistant HCC cells and NOTCH1 activation conferred hepatoma cells sorafenib resistance through enhanced self-renewal and tumorigenecity. Besides, the overexpression of EZH2 was required for the emergence of cancer stem cells following prolonged sorafenib treatment. As such, modulating EZH2 expression or activity suppressed activation of NOTCH1 pathway by elevating the expression of NOTCH1-related microRNAs, hsa-miR-21-5p and has-miR-26a-1-5p, via H3K27me3, and consequently weakened self-renewal ability and tumorigenecity and restored the anti-tumor effects of sorafenib. Overall, our results highlight the role of EZH2/NICD1 axis, and also suggest that EZH2 and NOTCH1 pathway are rational targets for therapeutic intervention in sorafenib-resistant HCC.
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Registered trials
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