We examined the transcriptional changes modulated by KDM1A inhibitor NCD-38 by performing global transcriptome analysis. Glioma Stem Cells (GSC10) were treated with either vehicle or NCD-38 for 24 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that NCD-38 modulated several genes that are involved in unfolded protein response, endoplasmic reticulum stress pathway and NRF-2 mediated oxidative stress response. Overall design: Total RNA was isolated from the GSC10 cells that were treated with vehicle or NCD-38 for 24 hours. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway.
Treatment, Subject
View SamplesThe expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.
Sex
View SamplesWe examined the transcriptional changes modulated by estrogen receptor beta (ERß) by performing global transcriptome analysis. U87 cells were transduced with lentiviral particles carrying either empty vector or ERß-FLAG expression vector and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that ERß modulated genes were related to homologous recombination, DNA damage response, ATM signaling and cell cycle pathways. Overall design: Total RNA was isolated from U87 cells expressing either empty vector or ERß expression vector. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat2. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways.
Cell line, Treatment, Subject
View SamplesWe examined the role of PELP1 in E2-ER-mediated transcription in the hippocampus under conditions of GCI by perfroming global transcriptome analysis. E2-treated FLOX and PELP1 FBKO mice were subjected to GCI followed by 24 h reperfusion and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that PELP1 is needed for optimal activation of E2-regulated genes following GCI. Overall design: Total RNA was isolated from the hippocampus of ovariectomized FLOX and PELP1 FBKO mice (implanted with E2 mini pumps) that were subjected to GCI followed by 24 h reperfusion. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Proline-, glutamic acid-, and leucine-rich protein 1 mediates estrogen rapid signaling and neuroprotection in the brain.
Specimen part, Cell line, Subject
View SamplesObjective:
Gene expression analysis in absence epilepsy using a monozygotic twin design.
Sex
View SamplesWe examined the transcriptional chagnes modulated by ECBI-11 by perfroming global transcriptome analysis. ZR75 cells were treated with either control or ECBI-11 in the presence of E2 for 48 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that ECBI modulated several genes that are involved in cell cycle, breast cancer signaling, estrogen signaling and apoptosis. Overall design: Total RNA was isolated from the ZR75 cells that were treated with vehicle or ECBI for 48 h. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers.
No sample metadata fields
View SamplesIn this study, we analyzed the effects of chronic alcohol consumption on liver repair and regeneration after partial hepatectomy (PHx). Rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced either by carbohydrate or by fat. After 5 weeks, rats were subjected to 70% PHx and liver samples were collected at 1, 6 and 24h after the surgery. The excised liver samples at t=0 served as within-animal controls. We used Affymetrix Rat Gene 1.0 ST arrays to obtain global gene expression data from each liver sample (n=4 replicate rats, 72 arrays total).
Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View SamplesAlcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. Here, we use the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4 wk incubation, cells were also tested for anchorage independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immuno-cytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype and mRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage independence in normal breast epithelial cells.
Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View SamplesAlcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. Here, we use the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4 wk incubation, cells were also tested for anchorage independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immuno-cytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype and mRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage independence in normal breast epithelial cells.
Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View Samples