ArticleGenes2021
Downregulation of Cell Cycle and Checkpoint Genes by Class I HDAC Inhibitors Limits Synergism with G2/M Checkpoint Inhibitor MK-1775 in Bladder Cancer Cells.
Article in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Largazole targets Musashi protein expression via miR-125b-5p and sensitizes triple-negative breast cancer cells to radiation.Frontiers in pharmacology · 2026Article
- HDAC2 as a therapeutic target in bladder cancer: insights into the altered epigenetic regulation and lysine lactylation.Journal of experimental & clinical cancer research : CR · 2025Article
- Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells.Scientific reports · 2025Article
- Dual molecular therapy targeting tumor cell heterogeneity improves therapeutic efficacy in glioblastoma.iScience · 2025Article
- Single-Cell and Bulk RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer.Journal of cellular and molecular medicine · 2025Article
- Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation.Annals of hematology · 2025Article
- Novel Histone Deacetylase (HDAC) Inhibitor Induces Apoptosis and Suppresses Invasion via E-Cadherin Upregulation in Pancreatic Ductal Adenocarcinoma (PDAC).Pharmaceuticals (Basel, Switzerland) · 2024Article
- New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.Journal of cellular and molecular medicine · 2024Article
- Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke.Science advances · 2024Article
- Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer.Cell death discovery · 2024Article
- HDAC-an important target for improving tumor radiotherapy resistance.Frontiers in oncology · 2023Review
- Epigenetic Priming and Development of New Combination Therapy Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.Cancers · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since genes encoding epigenetic regulators are often mutated or deregulated in urothelial carcinoma (UC), they represent promising therapeutic targets. Specifically, inhibition of Class-I histone deacetylase (HDAC) isoenzymes induces cell death in UC cell lines (UCC) and, in contrast to other cancer types, cell cycle arrest in G2/M. Here, we investigated whether mutations in cell cycle genes contribute to G2/M rather than G1 arrest, identified the precise point of arrest and clarified the function of individual HDAC Class-I isoenzymes. Database analyses of UC tissues and cell lines revealed mutations in G1/S, but not G2/M checkpoint regulators. Using class I-specific HDAC inhibitors (HDACi) with different isoenzyme specificity (Romidepsin, Entinostat, RGFP966), cell cycle arrest was shown to occur at the G2/M transition and to depend on inhibition of HDAC1/2 rather than HDAC3. Since HDAC1/2 inhibition caused cell-type-specific downregulation of genes encoding G2/M regulators, the WEE1 inhibitor MK-1775 could not overcome G2/M checkpoint arrest and therefore did not synergize with Romidepsin inhibiting HDAC1/2. Instead, since DNA damage was induced by inhibition of HDAC1/2, but not of HDAC3, combinations between inhibitors of HDAC1/2 and of DNA repair should be attempted.
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