Genome Wide Binding profile and transcriptome of STAT3 and STAT3 Mutant Y640F in STAT3 Wildtype and STAT3 Mutant Y640F hematopoietic progenitor cell lines
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211111 | GEO | 2023/01/25
REPOSITORIES: GEO
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Project description:Genome Wide Binding profile and transcriptome of STAT3 and STAT3 Mutant Y640F in STAT3 Wildtype and STAT3 Mutant Y640F hematopoietic progenitor cell lines
| PRJNA868941 | ENA
Project description:We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. We demonstrated that STAT3 has an important role in regulating, both positively and negatively, a diverse array of cellular processes, including cell adhesion, cytoskeletal remodeling, nucleotide, lipid and protein metabolism, as well as signal transduction. This suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. Balb/c-3T3 mouse fibroblasts, v-Src 3T3 cells and STAT3-C 3T3 cells were grown in DMEM/10% bovine calf serum supplemented with 1% penicillin and streptomycin. At each of 3 passages, cells from the five dishes were pooled and total RNA was extracted.
2011-09-08 | E-GEOD-22251 | biostudies-arrayexpress
Project description:STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted; sites within genes previously identified as STAT3-responsive by microarray analysis. The high percentage of sites able to bind STAT3 in vivo, as assessed by Chromatin Immunoprecipitation (ChIP) analysis, revealed the high predictive power of our method. Experiment Overall Design: Three prototypic situation were investigated using two replications for each experimental point: STAT3+/+ versus STAT3-/- MEFs , STAT3+/+ versus STAT3+/+ treated with OSM and STAT3-/- versus STAT3-/- treated with OSM.
2009-05-16 | E-GEOD-12262 | biostudies-arrayexpress
Project description:STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted sites within genes previously identified as STAT3-responsive by microarray analysis. The high percentage of sites able to bind STAT3 in vivo, as assessed by Chromatin Immunoprecipitation (ChIP) analysis, revealed the high predictive power of our method.
2009-05-05 | GSE12262 | GEO
Project description:Many patients have cancers that have increased activity of a protein called STAT3 that contributes critically to the development and growth of their cancer. Despite our knowledge of STAT3’s importance to cancer, scientists and doctors have not developed a drug that targets it and that patients can take to treat their cancer more effectively than treatments that are now available. Tvardi Therapeutics, Incorporated has developed a compound, TTI-101, which can be given by mouth and acts as a direct inhibitor of STAT3. Administration of TTI-101 to mice demonstrated that it blocked growth of cancers of the breast, head and neck, lung, and liver and it was safe when administered at high doses to mice, rats, and dogs. In this application, Tvardi is proposing to further develop TTI-101 for treatment of solid tumors for which the prognosis is dismal. The investigators will determine how safe it is when administered to patients with cancer, determine whether an adequate dose can be administered to patients with cancer that will block STAT3 in their cancer, and determine whether treatment with TTI-101 leads to reduced growth of their cancer.
| 2247646 | ecrin-mdr-crc
Project description:We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. We demonstrated that STAT3 has an important role in regulating, both positively and negatively, a diverse array of cellular processes, including cell adhesion, cytoskeletal remodeling, nucleotide, lipid and protein metabolism, as well as signal transduction. This suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis.
2011-09-09 | GSE22251 | GEO
Project description:We have previously shown that Kras mutant-induced lung tumors in CCSPCre/LSL-K-rasG12D mice (CC-LR) exhibited Stat3 activation. Here we sought to study the role of epithelial Stat3 in Kras-mutant lung tumor oncogenesis through derivation of a lung epithelial specific CC-LR/Stat3 conditional knockout (LR/Stat3D/D or LRDD) model. Analysis of tumor burdens revealed marked gender disparity following epithelial Stat3 deletion, LRDD males exhibited increased tumor burdens compared to male CC-LR animals whereas female LRDD mice displayed attenuated tumor development when compared to female CC-LR littermates. We then performed RNA-sequencing of whole lungs from the mice in order to understand global expression programs that may underlie this gender-specific effect of epithelial Stat3 deletion.
2018-12-26 | GSE109000 | GEO
Project description:Mass spectrometry analysis of proteins interacting with STAT3¬Flag was performed. STAT3-Flag was transiently expressed in HeLa cells and the interactome of STAT3-Flag was studied in lysosomal extracts. proteins co-¬immunoprecipitating with STAT3--Flag identified eight subunits of the vacuolar H+-¬ ATPase (V-¬ATPase) as potential STAT3 binding partners. Validation experiments were performed by antibody pull-down of STAT3.
2018-08-29 | PXD006788 | Pride
Project description:In the related study, to determine whether DUSP2 definitively served as a phosphatase for STAT3, an in vitro phosphatase assay was used. Using S-tag beads, p-STAT3 was pulled down from IL-6 stimulated HEK293T cells transfected with STAT3-S-Tag. DUSP2 or control protein, which was purified from HEK293T cells transfected with DUSP2-FLAG or empty vector through extraction with anti-FLAG beads and elution with FLAG peptides, were incubated with p-STAT3-S-Tag-beads in phosphatase buffer. Then bound proteins were eluted and subjected to MS analysis. When compared with the control, incubation of STAT3 and DUSP2 led to dephosphorylation of two STAT3 residues that have been reported to promote its activity, namely tyrosine 705 and serine 727.
2015-10-13 | PXD002743 | Pride
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