Project description:MCL cell lines were treated with aza and aza in combination with TSA. MCL cell lines were treated with aza and aza in combination with TSA. Gene expression following drug treatment was compared with untreated cells.
Project description:We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples when compared to normal B cells. Assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs (aza and TSA).
Project description:To understand the roles of DNA methylation and histone deacetylation in plant gene network that controls plant tolerance to freezing treatment, we used Affymetrix GeneChips ATH-121501 to analysis. For microarray analysis, Arabidopsis (ecotype Columbia) seedlings grew in four types of sterile growth medium: no any other modifying agents, added 7g/ml 0.5 M aza-dC in water (DNA methylation inhibitor), added TSA in methanol (histone deacetylation inhibitor), both aza-dC and TSA, all for 16 day in growth chamber (16-h day length at 70% relative humidity, 23 M-BM-0C) , then all seedlings were cold treated at 0 M-BM-0C for 24 h in growth chamber (16-h day length at 70% relative humidity). A total of 3305 genes expression were statistically analysized. Our study provides some clues that the transcript levels of some cold-responsive genes regulated by DNA methylation and histone deacetylation. This will be valuable for understanding gene regulation by epigenetic modifications under freezing stress. Keywords: Cold Stress response, DNA methylation, histone deacetylation Three replicates for aza-dc and TSA treatment, and two replicates for Mock and both aza-dc and TSA treatment. All samples were treated 0M-BM-0C 24h.
Project description:Epigenetic alterations are a fundamental aspect of cancer cells, and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which points to sensitivity towards epigenetic drugs in this patient group. The young age of these patients is accompanied by However, ongoing developmental processes regulated by epigenetic mechanisms may be deregulated by epigenetic drugs in this patient group that is characterized by young age. This prompted us to study molecular effects and side-effects of low dosage epigenetic drugs in neuro-ectodermal tumor cell lines of pediatric origin. Short term combination treatment of 5-aza-2`-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages reduced proliferation, induced wide-spread demethylating effects in 17 NBL and 5 PNET cell lines, and was accompanied by large effects on gene-expression profiles. Approximately half of the genes that were significantly upregulated upon treatment demonstrated significant demethylating effects in their promoter regions. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a limited number of imprinted genes, but also known tumor suppressor genes and oncogenes. In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. This treatment affected more than 97% of cellular pathways investigated and further studies towards the effectiveness and side-effects of epigenetic drugs are desirable in pediatric tumors. Epigenetic alterations are a fundamental aspect of cancer cells, and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which points to sensitivity towards epigenetic drugs in this patient group. The young age of these patients is accompanied by However, ongoing developmental processes regulated by epigenetic mechanisms may be deregulated by epigenetic drugs in this patient group that is characterized by young age. This prompted us to study molecular effects and side-effects of low dosage epigenetic drugs in neuro-ectodermal tumor cell lines of pediatric origin. Short term combination treatment of 5-aza-2`-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages reduced proliferation, induced wide-spread demethylating effects in 17 NBL and 5 PNET cell lines, and was accompanied by large effects on gene-expression profiles. Approximately half of the genes that were significantly upregulated upon treatment demonstrated significant demethylating effects in their promoter regions. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a limited number of imprinted genes, but also known tumor suppressor genes and oncogenes. In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. This treatment affected more than 97% of cellular pathways investigated and further studies towards the effectiveness and side-effects of epigenetic drugs are desirable in pediatric tumors.
Project description:The goal of this study is to identify the gene expression changes caused by exposure of to the DNMT inhibitor 5-aza-2'-deoxycytidine (5Aza) and HDAC inhibitor Trichostatin A (TSA). We performed rRNA-depleted RNA sequencing of the untreated and drug-treated MCF7 breast cancer cell lines and carried out differential gene expression analysis. Although 5Aza caused a stranger demethylation effect than TSA, there were fewer differentially expressed gene in the 5Aza-treated MCF7 than the TSA-treated cells.
Project description:Abstract: Epigenetic alterations are a fundamental aspect of cancer cells, and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which makes the introduction of epigenetic drugs in this patient category logical. However, the young age of these patients is accompanied by ongoing developmental processes which are regulated epigenetic mechanisms, and prompted us to study molecular effects of nanomolar dosage epigenetic drugs in neuro-ectodermal tumor cell lines. Combination treatment of 5-aza-2`-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages resulted in wide-spread demethylating effects in 17 NBL and 5 PNET cell lines in vitro. This widespread demethylation had large effects on gene-expression profiles. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a few imprinted genes. Integration analysis of CpG island methylation array data and whole genome gene expression data identified 30 genes potentially upregulated by gene promoter demethylation. Homeobox genes frequently showed demethylation in both short term (72 hours) and long term cultures (3 months) of NBL lines. Continuous treatment with epigenetic drugs resulted in low rates of proliferation. The low rate of proliferation that might explain limited consecutive demethylation upon prolonged exposure. In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. These effects affected more than 97% of cellular pathways investigated. Further studies towards the effects of epigenetic drug combinations are advised before being applied in clinical trials for pediatric patients.
Project description:The goal of this study is to identify the DNA methylation changes caused by exposure of to the DNMT inhibitor 5-aza-2â-deoxycytidine (5Aza) and HDAC inhibitor Trichostatin A (TSA). We performed whole-genome bisulfite sequencing of the drug-treated MCF7 breast cancer cell lines and compare their DNA methylation profile with the untreated MCF7 (see E-MTAB-2014). While MCF7 treated with both drugs experienced global loss of DNA methylation, the 5Aza induced stronger demethylation than TSA.
Project description:Expression data from pancreatic cancer cell lines and non-neoplastic pancreatic cell line HPDE To identify genes epigenetically silenced and regulated in pancreatic cancer We compared the gene expression profiles of 6 pancreatic cancer cell lines (panc215, A32-1, A38-5, panc2.5, panc2.8, and panc3.014), to the non-neoplastic pancreas cell line, HPDE. We also compared the baseline gene expression of the pancreatic cancer cell lines to expression patterns after treatment with 5-aza-dC alone, TSA alone, and to a combination of 5-aza-dC/TSA.
Project description:To understand the roles of DNA methylation and histone deacetylation in plant gene network that controls plant tolerance to freezing treatment, we used Affymetrix GeneChips ATH-121501 to analysis. For microarray analysis, Arabidopsis (ecotype Columbia) seedlings grew in four types of sterile growth medium: no any other modifying agents, added 7g/ml 0.5 M aza-dC in water (DNA methylation inhibitor), added TSA in methanol (histone deacetylation inhibitor), both aza-dC and TSA, all for 16 day in growth chamber (16-h day length at 70% relative humidity, 23 °C) , then all seedlings were cold treated at 0 °C for 24 h in growth chamber (16-h day length at 70% relative humidity). A total of 3305 genes expression were statistically analysized. Our study provides some clues that the transcript levels of some cold-responsive genes regulated by DNA methylation and histone deacetylation. This will be valuable for understanding gene regulation by epigenetic modifications under freezing stress. Keywords: Cold Stress response, DNA methylation, histone deacetylation
Project description:DNA methylation analysis in oropharyngeal squamous carcinoma(OPSCC) samples, oropharyngeal non-cancerous mucosa samples and head and neck cancer cell lines, FaDu and UMSCC47 before and after 5-aza'2-deoxycytidine(Aza)/trichostatin A(TSA) treatment. Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across 485,577 CpG sites. Samples included 13 OPSCC samples, 4 non-cancerous mucosa samples and 2 FaDu with and without Aza/TSA treatment and 2 UMSCC47 with and without Aza/TSA treatment.