ArticleEuropean journal of medical research2016
HDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma.
Article in European journal of medical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Recent Advancements in the Development of HDAC/Tubulin Dual-Targeting Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lentinan progress in inflammatory diseases and tumor diseases.European journal of medical research · 2024Review
- Molecular Targets of Valeric Acid: A Bioactive Natural Product for Endocrine, Metabolic, and Immunological Disorders.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Profiles of Acetylation Regulation Genes Contribute to Malignant Progression and Have a Clinical Prognostic Impact on Liver Cancer.Disease markers · 2022Article
- Roles and regulation of histone acetylation in hepatocellular carcinoma.Frontiers in genetics · 2022Review
- Improved Anticancer Activities of a New Pentafluorothio-Substituted Vorinostat-Type Histone Deacetylase Inhibitor.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma.Translational cancer research · 2021Article
- Pharmacological inhibition of HDAC1/3-interacting proteins induced morphological changes, and hindered the cell proliferation and migration of hepatocellular carcinoma cells.Environmental science and pollution research international · 2021Article
- Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.Journal of personalized medicine · 2021Review
- Histone Deacetylase Inhibitors, Intrinsic and Extrinsic Apoptotic Pathways, and Epigenetic Alterations of Histone Deacetylases (HDACs) in Hepatocellular Carcinoma.Iranian journal of pharmaceutical research : IJPR · 2021Article
- Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor.Molecular therapy oncolytics · 2020Article
- Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors.International journal of molecular sciences · 2020Article
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- RNA-seq analysis identifies cytoskeletal structural genes and pathways for meat quality in beef.PloS one · 2020Article
- Suberoylanilide hydroxamic acid upregulates histone acetylation and activates endoplasmic reticulum stress to induce apoptosis in HepG2 liver cancer cells.Oncology letters · 2019Article
- Class I-Histone Deacetylase (HDAC) Inhibition is Superior to pan-HDAC Inhibition in Modulating Cisplatin Potency in High Grade Serous Ovarian Cancer Cell Lines.International journal of molecular sciences · 2019Article
- Review
- Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes.Cancer genomics & proteomicsArticle
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistone deacetylation, a common hallmark in malignant tumors, strongly alters the transcription of genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have previously shown that HDAC1, HDAC2, and HDAC3 (HDAC1-3) genes encoding histone deacetylases 1-3 are upregulated in primary human hepatocellular carcinoma (HCC). The aim of this study was to characterize the functional effects of HDAC1-3 downregulation and to identify functionally important target genes of histone deacetylation in HCC.
methodsTherefore, HCC cell lines were treated with the histone deacetylase inhibitor (HDACi) trichostatin A and by siRNA-knockdown of HDAC1-3. Differentially expressed mRNAs were identified after siRNA-knockdown of HDAC1-3 using mRNA expression profiling. Findings were validated after siRNA-mediated silencing of HDAC1-3 using qRTPCR and Western blotting assays.
resultsmRNA profiling identified apoptotic protease-activating factor 1 (Apaf1) to be significantly upregulated after HDAC inhibition (HLE siRNA#1/siRNA#2 p < 0.05, HLF siRNA#1/siRNA#2 p < 0.05). As a component of the apoptosome, a caspase-activating complex, Apaf1 plays a central role in the mitochondrial caspase activation pathway of apoptosis. Using annexin V, a significant increase in apoptosis could also be shown in HLE (siRNA #1 p = 0.0034) and HLF after siRNA against HDAC1-3 (Fig. 3a, b). In parallel, caspase-9 activity was increased after siRNA-knockdown of HDAC1-3 leading to enhanced apoptosis after HDAC inhibition (Fig. 3c, d).
conclusionsThe present data show that siRNA-knockdown of HDAC1-3 plays a major role in mediating apoptotic response to HDAC inhibitors through regulation of Apaf1.
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