Transcription profiling of oesophageal adenocarcinoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): 418 [Affymetrix]
ORGANISM(S): Homo sapiens
SUBMITTER: Leo Zeef
PROVIDER: E-MTAB-5163 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Viral dsRNA binds to Retinoic acid Inducible Gene I (RIG-I) Like Receptors (RLRs), promoting the production of Interferon (IFN). Interferon then stimulates the innate and adaptive immune system in an autocrine and paracrine manner. Outside of conical pathways, regulators of the interferon (IFN) activation/response system are poorly characterized. In this study, we used a discovery-biased approach to identify Kinases that are part of the interferon system. Differential changes in phosphorylation sites, in the context of dsRNA RIG-I stimulation, were identified with unbiased mass-spec biased phospho-proteomics. We then computationally identified several Kinases upregulated after RIG-I stimulation from phospho-proteomics data. A Chemoproteomics screen was then used to characterize the altered interferon response in the presence of Kinases inhibitors for the upregulated kinases. Combining unbiased phosphoproteomics with a chemoproteomics screen, we identified several potentially novel regulators of the Interferon system whose inhibition blocked the production of Interferon Stimulated Genes.
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Project description:These experiments were conducted as part of a study to derive the targets of miRNAs (See also E-MTAB-418). Two independent BayGenomics mouse embryonic stem cell lines (XH157 and XG058), each bearing a gene trap between exons 9 and 10 of the Dgcr8 locus (ENSMUST00000115633, Ensembl v53) were further mutagenised by the targetted insertion of a second Dgcr8 gene trap cassette. Consequently two independent heterozygous and two independent homozygous mutant Dgcr8 cells were derived (Dgcr8tm1,gt1/+, Dgcr8tm1,gt2/+, Dgcr8gt1/tm1 and Dgcr8gt2/tm1). Subsequently individual miRNA mimics were reintroduced into the Dgcr8-depleted background. In this set of experiments, cells were allowed to recover for 10 hours. The effect of the miRNA on the mRNA expression of the cells was assessed through the comparison of the expression profile of the transfected cells to that of cells transfected with a control mimic, which had recovered over the same period. This allows the roles of individual miRNAs to be investigated.
2012-08-20 | E-MTAB-968 | biostudies-arrayexpress
Project description:ATAC-seq in oesophageal cell lines, OE33 (OAC), FLO1 (OAC), HET1A (Normal)
2016-09-12 | E-MTAB-4209 | biostudies-arrayexpress
Project description:The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as androgen receptor trapped clone-27 (ART-27). The impact of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are upregulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Experiment Overall Design: Steroid-deprived LNCaP cells were transfected with control or ART-27 siRNA and stimulated with ethanol vehicle or 10 nM R1881 for 18 hrs. 8 samples, 4 conditions, 2 replicates per condition.
2009-06-08 | E-GEOD-14043 | biostudies-arrayexpress
Project description:Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer which is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood although genomic sequencing studies have identified several genes encoding chromatin remodeling enzymes that are frequently mutated in OAC. This finding is consistent with the knowledge that one important change that occurs in cancer cells is a reprogramming of the chromatin environment which leads to subsequent changes in their transcriptional profile.
2017-07-07 | E-MTAB-5175 | biostudies-arrayexpress
Project description:Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC) and BarrettM-bM-^@M-^Ys adenocarcinomas (BAC) revealed similar STAT3 expression in ESCCs and BACs, but preferentially activated P-STAT3 in ESCCs. In vitro, strong STAT3 activation was seen by EGF-stimulation in OE21 (ESCC) cells, whilst OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 and OE33 cells and reduced cell migration in OE33, but not in OE21 cells. Transcriptome analysis identified STAT3-knockdown associated down-regulation of cell cycle processes and the selective down-regulation of cyclins and cyclin dependent kinaes associated genes in both OE21 and OE33 cells. Moreover, the transcriptome response showed changes in cell migration/invasion related genes that correlated with the associated phenotype measurements. This study demonstrates the importance of STAT3 expression and activation in esophageal carcinomas, whereby the extent differs between ESCCs and BACs. STAT3 knockdown significantly reduces cell proliferation in both types of esophageal cancer cells and inhibits migration in BAC cells. Thus, STAT3 may be further exploited as potential novel therapeutic target for esophageal cancers. The effect of STAT3 knock-down in OE33 and OE21 cells was calculated from three biologically independent experiments. 3x10e4 cells were seeded in triplicate in 24 well-plates and were transfected with twice 100nM STAT3 siRNA (pool of 4 STAT3 sequences, siGENOMEM-BM-.SMARTpoolM-BM-., Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) or SilencerM-BM-. negative siRNA control (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) using 1M-BM-5l DharmaFECT (Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) transfection reagent for OE33 cells or siPORTTM NeoFXTM (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) transfection reagent for OE21 cells. Differential gene regulation was quantified 72 hours after the first transfection by comparing separately for the OE21 and OE33 cells the STAT3 siRNA replicates and the respective cell lines containing the scrambled siRNA vector.
2013-06-16 | E-GEOD-47763 | biostudies-arrayexpress
Project description:Follicular lymphoma (FL) is the most common indolent subtype of non-Hodgkinâs lymphoma, with relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, 20-60% of FL patients undergo transformation to aggressive diffuse large B cell lymphoma (DLBCL), with a reduced median survival of about 1.2 years. The specific functional and genetic determinants of FL transformation are still elusive and only a relatively small fraction of the cases is accounted for by established, recurrent alterations in TP53, MYC and BCL6, inactivation of CDKN2A and CDKN2B, or amplification of REL. We addressed this deficiency by performing systematic analysis of a B cell specific regulatory model with FL transformation signatures, using the Master Regulator Inference algorithm (MARINa). We show that the candidate master regulators inferred by the algorithm in FL induce synthetic lethality in DLBCL cells and lead to identification of specific compound combinations inducing synergistic loss of viability in transformed DLBCL cells RNA was obtained from 45 samples, which included siRNA silencing of 5 single transcription factors, 5 combinations of two transcription factors and non-target control in triplicates.
2015-11-11 | E-GEOD-66714 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-08 | E-GEOD-62178 | biostudies-arrayexpress
Project description:We identified LAMP3 as a key driver gene of anti-viral subnetwork genes in cervical cancer patients. Therefore we tested this prediction using an in vitro system. This is the first direct demonstration of LAMP3 regulatory role in interferon-dependent immune response. We first pretreated HeLa cells with control siRNA or LAMP3 siRNA overnight and then added 1 ng/ml of interferon alpha to the cultures for 3 and 4 days
2011-12-29 | E-GEOD-29009 | biostudies-arrayexpress
Project description:Mouse models of cancer recapitulate many of the molecular and biological features of the human disease. We sought to exploit these experimental merits in a systematic comparative proteomics search for circulating proteins associated with lung tumor development. In-depth quantitative proteomics was applied to plasmas from three mouse models of lung adenocarcinoma driven by mutant EGFR or Kras or induced by urethane exposure and a mouse model of small cell lung cancer driven by loss of Trp53 and Rb. To further refine our lung cancer-specific and broad carcinoma signatures, we intersected these lung cancer proteome profiles with those from other well-established mouse models of pancreatic, ovarian, colon, prostate and breast cancer, as well as two mouse models of inflammation. A set of proteins regulated by Titf1/Nkx2-1, a master transcription factor in cells from the peripheral airways and a known lineage-survival oncogene in lung cancer was identified in plasmas of mouse models of lung adenocarcinoma. An EGFR network of proteins was discerned in the plasma of mice with lung tumors driven by a mutant human EGFR. Levels of these proteins returned toward baseline upon treatment with a tyrosine kinase inhibitor. Moreover, a distinct plasma signature was uncovered in the Trp53/Rb mutant small cell lung cancer model that included a set of proteins associated with neuroendocrine development. Our studies have identified novel plasma protein signatures among molecularly or histopathologically defined lung cancer subtypes. siRNA transfection experiments were performed in NCI-H3255 and HCC4019 lung adenocarcinoma cell lines using ON-TARGETplus SMARTpool small interfering RNAs (siRNAs) targeting TITF1 (L-019105-01-0005) along with a negative control (ON-TARGETplus siCONTROL nontargeting siRNA pool; D-001810-10-05) obtained from Dharmacon. 400000 cells were seeded in antibiotic-free RPMI-1640 media supplemented with 10% FBS, in 6-well culture plates. The next day, cells were transfected at a final concentration of 100nM siRNA using 6ul DharmaFECT 1 (Dharmacon) according to the manufacturer's instructions. 72-hours post-transfection, RNA was harvested using Trizol (Invitrogen) and protein using RIPA buffer for microarray expression and western blotting, respectively. RNA from TITF1 knockdown and control experiments was profiled by the MSKCC Genomics Core using the Illumina Human HT-12 v3.0 array platform according to manufacturer's instructions. Two biological replicates were profiled for each condition. Resulting data files were exported using GenomeStudio software, log2 transformed, quantile-normalized and analyzed using Partek Genomics Suite (v6.5). Average values of replicates for each gene were then compared between the TITF1 knockdown and non-targeting treatments for each cell line to identify candidate TITF1 regulated genes.
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