Microarray gene expression profiling reveals potential mechanisms of tumor suppression by the class I HDAC-selective benzoylhydrazide inhibitors.

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A novel class of HDIs with a previously undescribed benzoylhydrazide scaffold has been discovered through a high throughput screening campaign. Using microarray profiling of gene expression, we have previously demonstrated that treatment of breast cancer cells with a lead benzoylhydrazide HDI UF010 results in cell cycle arrest and apoptosis, likely through activation of tumor suppression pathways with concurrent inhibition of oncogenic pathways. In this brief report, we show methodological and analytical details and discuss additional pathways such as immune signaling that are affected by UF010. Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes were identified using the Limma package with a Benjamini and Hochberg false discovery rate multiple testing correction. Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26217556", "locator": "sections[8] \"Microarray data quality control and analysis\" paragraph 2", "quote": "Differentially expressed genes were identified using the Limma package with a Benjamini and Hochberg false discovery rate multiple testing correction."}, {"asset": "source:pmid:26217556", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26217556", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using Limma with Benjamini–Hochberg false-discovery-rate correction, the study found that the benzoylhydrazide HDI UF010 induces gene activation and repression; the raw and processed microarray data were deposited in NCBI’s Gene Expression Omnibus under accession GSE56823.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26217556", "locator": "sections[10] \"Results\" paragraph 2", "quote": "Analyses of the microarray dataset reveal that the benzoylhydrazide HDI UF010 induces gene activation and repression, consistent with findings by others that HDIs can up and downregulate gene expression [7], [8], [9], [10], [11], [12]."}, {"asset": "source:pmid:26217556", "locator": "sections[8] \"Microarray data quality control and analysis\" paragraph 2", "quote": "Differentially expressed genes were identified using the Limma package with a Benjamini and Hochberg false discovery rate multiple testing correction."}, {"asset": "source:pmid:26217556", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Raw and processed data from the microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under the accession number: GSE56823."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using Limma with Benjamini–Hochberg false-discovery-rate correction, the study found that the benzoylhydrazide HDI UF010 induces gene activation and repression; the raw and processed microarray data were deposited in NCBI’s Gene Expression Omnibus under accession GSE56823.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26217556"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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