Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA257522 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The identification of proteins that change in response to a drug perturbation can shed light on the molecular mechanisms of the drug and its potential use in therapies. Histone deacetylases (HDACs) are targets for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is an FDA approved HDAC inhibitor used for the treatment of cutaneous T-cell lymphoma. ING2 is a non-catalytic component of the Sin3/HDAC complex. To obtain a better mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its protein-protein interaction network and identified a mutually exclusive pair within the complex. We then assessed the effects of SAHA on the disruption of the complex network through six homologous baits. SAHA perturbs multiple protein interactions and therefore compromises the composition of large parts of the Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene expression in breast cancer cells to a knockdown of the ING2 subunit indicated that a portion of the anticancer effects of SAHA may be attributed to the disruption of ING2's association with the complex. Cells from human breast cancer cell line MDA-MB-231 were treated with the HDAC inhibitor drug SAHA in duplicate and compared to a DMSO vehicle control in triplicate, for a total of 5 samples.
2014-09-01 | E-GEOD-60124 | biostudies-arrayexpress
Project description:The Sin3/HDAC multi-protein complex consists of at least 17 subunits and is known to have roles in diverse biological and cellular processes including transcription, chromatin structure, and the cell cycle. ING2 is a non-catalytic component of this complex. To obtain a better mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its protein-protein interaction network and identified a mutually exclusive pair within the complex. Suberoylanilide hydroxamic acid (SAHA) is an FDA approved HDAC inhibitor used for the treatment of cutaneous T-cell lymphoma. We assessed the effects of SAHA on the disruption of the complex network through six homologous baits. SAHA perturbs multiple protein interactions and therefore compromises the composition of large parts of the Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene expression in breast cancer cells to a knockdown of the ING2 subunit indicated that a portion of the anticancer effects of SAHA may be attributed to the disruption of ING2âs association with the complex. ING2 siRNA knockdowns in human breast cancer cell line MDA-MB-231 were compared to a non-targeting control in triplicate, for a total of 6 samples.
2014-09-01 | E-GEOD-60123 | biostudies-arrayexpress
Project description:The identification of proteins that change in response to a drug perturbation can shed light on the molecular mechanisms of the drug and its potential use in therapies. Histone deacetylases (HDACs) are targets for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is an FDA approved HDAC inhibitor used for the treatment of cutaneous T-cell lymphoma. ING2 is a non-catalytic component of the Sin3/HDAC complex. To obtain a better mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its protein-protein interaction network and identified a mutually exclusive pair within the complex. We then assessed the effects of SAHA on the disruption of the complex network through six homologous baits. SAHA perturbs multiple protein interactions and therefore compromises the composition of large parts of the Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene expression in breast cancer cells to a knockdown of the ING2 subunit indicated that a portion of the anticancer effects of SAHA may be attributed to the disruption of ING2's association with the complex.
2014-09-01 | GSE60124 | GEO
Project description:The Sin3/HDAC multi-protein complex consists of at least 17 subunits and is known to have roles in diverse biological and cellular processes including transcription, chromatin structure, and the cell cycle. ING2 is a non-catalytic component of this complex. To obtain a better mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its protein-protein interaction network and identified a mutually exclusive pair within the complex. Suberoylanilide hydroxamic acid (SAHA) is an FDA approved HDAC inhibitor used for the treatment of cutaneous T-cell lymphoma. We assessed the effects of SAHA on the disruption of the complex network through six homologous baits. SAHA perturbs multiple protein interactions and therefore compromises the composition of large parts of the Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene expression in breast cancer cells to a knockdown of the ING2 subunit indicated that a portion of the anticancer effects of SAHA may be attributed to the disruption of ING2’s association with the complex.
2014-09-01 | GSE60123 | GEO
Project description:Histone deacetylases (HDACs) regulate gene expression. Inhibition of class I HDACs has been shown to inhibit cancer cell growth. Largazole, a new potent HDAC inhibitor, shows strong antitumor activity, presumably by modulating transcription of cancer relevant genes. We used microarray analysis of human HCT116 colorectal carcinoma cell line to determine the gene expression profile after largazole treatment in comparison with other HDAC inhibitors (FK228 and SAHA). The goal was to identify regulated genes that can be linked to the antiproliferative effects of these HDAC inhibitors in HCT116 cells. To characterize the genes regulated by Largazole, SAHA and FK228, genome-wide gene expression analysis was carried out. Human HCT116 colorectal carcinoma cells (400,000) were seeded per well (6-well dish) and one day later treated with Largazole, SAHA, FK228 and vehicle control. 10 h later, total RNA was extracted and processed for hybridization to an Affymetrix Human Genome U133 2.0 GeneChip. Global alterations in transcript levels upon Largazole, SAHA and FK228 treatment were determined through comparison with data derived from cells treated with vehicle control. The experiment was carried out in duplicate.
2010-08-28 | E-GEOD-22061 | biostudies-arrayexpress
Project description:Abnormal activities of histone lysine demethylases (KDMs) and lysine deacetylases (HDACs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms underlying the crosstalk between KDMs and HDACs in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDACs, but not NAD+ dependent class III HDACs, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer. Twelve samples were subject to microarray anaylsis: 3 biological replicates were treated for 24h with 1)DMSO, 2) 5uM SAHA (suberanilohydroxamic acid), 3) 2.5mM Pargyline or 4) 5uM SAHA + 2.5mM Pargyline.
2015-09-04 | E-GEOD-72688 | biostudies-arrayexpress
Project description:HDAC inhibitor SAHA reverses inflammatory gene expression in diabetic endothelial cells
| PRJNA309443 | ENA
Project description:Histone deacetylases (HDACs) regulate gene expression. Inhibition of class I HDACs has been shown to inhibit cancer cell growth. Largazole, a new potent HDAC inhibitor, shows strong antitumor activity, presumably by modulating transcription of cancer relevant genes. We used microarray analysis of human HCT116 colorectal carcinoma cell line to determine the gene expression profile after largazole treatment in comparison with other HDAC inhibitors (FK228 and SAHA). The goal was to identify regulated genes that can be linked to the antiproliferative effects of these HDAC inhibitors in HCT116 cells.
2010-08-28 | GSE22061 | GEO
Project description:Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. OSU-HDAC-44 was a pan-HDAC inhibitor and exhibits 3-4 times more effectiveness than suberoylanilide hydroxamic acid (SAHA) in suppressing cell viability in various NSCLC cell lines. Upon OSU-HDAC-44 treatment, mitosis and cytokinesis were inhibited and subsequently led to mitochondria-mediated apoptosis. The cytokinesis inhibition resulted from OSU-HDAC-44-mediated degradation of mitosis and cytokinesis regulators Auroroa B and survivin. The deregulation of F-actin dynamics induced by OSU-HDAC-44 was associated with reduction in RhoA activity resulting from srGAP1 induction. Chromatin-immunoprecipitation-on-chip analysis revealed that OSU-HDAC-44 induced chromatin loosening and facilitated transcription of genes involved in crucial signaling pathways such as apoptosis, axon guidance and protein ubiquitination. Finally, OSU-HDAC-44 efficiently inhibited A549 xenograft tumor growth and induced acetylation of histone and non-histone proteins and apoptosis in vivo. Collectively, our data provide compelling evidence that OSU-HDAC-44 is a potent HDAC targeted inhibitor and can be tested for NSCLC chemotherapy. ChIP-chip analysis for H3K9K14ac in A549, H1299 and CL1-1 lung cancer cells treated with 2.5 uM histone deacetylase inhibitor, OSU-HDAC-44, for 2 hours.
2010-12-22 | E-GEOD-20304 | biostudies-arrayexpress
Project description:Comparison of miRNA expression profiles in SKBr3 breast cancer cells treated with HDAC inhibitor LAQ-824 vs. untreated SKBr3 cells. Keywords: Expression profiling of pharmacological response to HDAC inhibitor
2006-02-01 | GSE3798 | GEO