Epigenetic Regulation of Apoptosis and Cell Cycle Regulatory Genes in Human Colon Carcinoma Cells.

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We have identified verticillin A from Verticillium-infected wild mushrooms as a potent anti-cancer agent that effectively suppresses 5-FU-resistant human colon cancer cells. Interestingly, a sublethal dose of verticillin A also acts as a potent sensitizer that overcomes human colon carcinoma cell resistance to FasL- and TRAIL-induced apoptosis. To identify verticillin A-regulated genes, we performed a genome-wide gene expression analysis and identified 1287 genes whose expression levels were either up- or down-regulated 1.5 fold. Forty-six of these genes have known function in regulation of apoptosis, and ninety genes have function in cell cycle regulation. Our recent study has identified verticillin A as a selective histone methyltransferase inhibitor. These identified genes are thus potential molecular targets for epigenetic-based therapy to overcome human colon cancer 5-FU resistance. The entire dataset is deposited in the NIH GEO database. 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The headline result was the identification of 1,287 genes whose expression was up- or downregulated by at least 1.5-fold.", "kind": "quantitative", "target": {"value": 1.5, "unit": "fold change", "tolerance": null, "source": "Using a 1.5 fold change and p value less than 0.01, we have identified 1287 genes whose expression levels were either up- or down-regulated 1.5 fold."}, "evidence": [{"asset": "source:pmid:26309812", "locator": "sections[3] \"Experimental design, materials and methods\" paragraph 2", "quote": "Differential expressions were calculated using ANOVA of Partek package."}, {"asset": "source:pmid:26309812", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The entire dataset is deposited in the NIH GEO database; accession number GSE51262."}, {"asset": "source:pmid:26309812", "locator": "sections[2] \"Direct link to deposited data\" paragraph 2", "quote": "http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51262."}, {"asset": "source:pmid:26309812", "locator": "sections[3] \"Experimental design, materials and methods\" paragraph 3", "quote": "Using a 1.5 fold change and p value less than 0.01, we have identified 1287 genes whose expression levels were either up- or down-regulated 1.5 fold."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differential expression was calculated using ANOVA, and the source data are available through the NIH GEO dataset GSE51262 at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51262. 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