ArticleBMC cancer2016
HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma.
Article in BMC cancer, 2016. 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, 49 citations in OpenAlex.
- Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: a multicentre, single-arm phase I/II clinical trial.British journal of cancer · 2017Trial
- Machine learning-driven classification and prognostic prediction of kidney renal clear cell carcinoma using APOBEC family expression signatures.Scientific reports · 2025Article
- M344 Suppresses Histone Deacetylase-Associated Phenotypes and Tumor Growth in Neuroblastoma.International journal of molecular sciences · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug.Pharmaceutics · 2025Article
- Article
- WTAP-dependent N6-methyladenosine methylation of lncRNA TEX41 promotes renal cell carcinoma progression.Scientific reports · 2024Article
- Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells.Cancers · 2024Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- Speckle-type POZ protein could play a potential inhibitory role in human renal cell carcinoma.BMC cancer · 2022Article
- A Data Science Approach for the Identification of Molecular Signatures of Aggressive Cancers.Cancers · 2022Article
- Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma.Frontiers in pharmacology · 2022Article
- The Potential Role of Mitochondrial Acetaldehyde Dehydrogenase 2 in Urological Cancers From the Perspective of Ferroptosis and Cellular Senescence.Frontiers in cell and developmental biology · 2022Review
- Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia.Diagnostics (Basel, Switzerland) · 2021Review
- Targeting Histone Modifications in Bone and Lung Metastatic Cancers.Current osteoporosis reports · 2021Review
- Article
- The roles of histone deacetylases in kidney development and disease.Clinical and experimental nephrology · 2021Review
- SOX4 maintains the stemness of cancer cells via transcriptionally enhancing HDAC1 revealed by comparative proteomics study.Cell & bioscience · 2021Article
- Review
- Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundClass I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown.
methodsFour isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student's T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival.
resultsOur analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset.
conclusionsTaking together, these results suggest that HDAC1 and HDAC6 may play a role in ccRCC biology and could represent rational therapeutic targets.
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