ArticlePloS one2021
CHD4 regulates platinum sensitivity through MDR1 expression in ovarian cancer: A potential role of CHD4 inhibition as a combination therapy with platinum agents.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Urothelial-lineage master transcription factor hub proteomics shows mechanisms impeding urothelial cancer cell differentiation.bioRxiv : the preprint server for biology · 2026Article
- Role of CHD4 in tumor progression, DNA damage response and treatment resistance (Review).Oncology reports · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death.Cell chemical biology · 2024Article
- USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer.Cell death & disease · 2024Article
- SMARCA5-mediated chromatin remodeling is required for germinal center formation.The Journal of experimental medicine · 2024Article
- iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis.Genome biology · 2024Article
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- Gene amplification of chromatin remodeling factorOncology letters · 2024Article
- CHD4 acts as a prognostic factor and drives radioresistance in HPV negative HNSCC.Scientific reports · 2024Article
- Interactions of Histone Deacetylase 6 with DNA Damage Repair Factors Strengthen its Utility as a Combination Drug Target in High-Grade Serous Ovarian Cancer.ACS pharmacology & translational science · 2023Article
- Resistance Improvement and Sensitivity Enhancement of Cancer Therapy by a Novel Antitumor Candidate onto A2780 CP and A2780 S Cell Lines.Reports of biochemistry & molecular biology · 2023Article
- Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes.Diabetes & metabolism journal · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- The Emerging Role of Chromatin Remodeling Complexes in Ovarian Cancer.International journal of molecular sciences · 2022Review
- Comprehensive analysis of the expression, prognosis, and immune infiltrates for CHDs in human lung cancer.Discover oncology · 2022Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival. CHD4 mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.
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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.