Gene induction by the USP6 oncogene in response to interferon
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107307 | GEO | 2018/01/24
REPOSITORIES: GEO
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Project description:Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma. A673 Ewing cell line was treated for 72 hours by either control siRNA or siRNA directed against PRKCB or EWSR1-FLI1. Total RNAs were extracted and hybridized on HuGene1.1STv1 Affymetrix Arrays. Normalisation was performed using specific Brainarray Enrtez gene CDF file (v14.1).
2012-06-30 | E-GEOD-38392 | biostudies-arrayexpress
Project description:Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma.
2012-07-01 | GSE38392 | GEO
Project description:Primary pediatric Ewing sarcoma (ES), one uncharacterized sarcoma as well as primary and well established ES cell lines were compared to probes of different normal tissues 8 Ewing sarcoma patient samples (MuET-x), 3 primary ES cell lines (SB-KMS-y), 3 well established ES cell lines (A673, SK-N-MC, RD-ES) and 22 normal tissues (PBMC, spleen, thymus, stomach, ...., uterus, fetal brain, fetal liver) were analyzed.
2013-05-01 | E-GEOD-45544 | biostudies-arrayexpress
Project description:Purpose: Our experimental results demonstrate an essential role for the lncRNA HOTAIR in Ewing sarcoma. We have repressed HOTAIR expression in three Ewing sarcoma cell lines and overexpressed HOTAIR, alone and with EWS-FLI1, in htert-immortalized human mesenchymal stem cells to evaluate its effects on gene expression in this cancer. Methods: RNA-Seq of Ewing sarcoma cell lines with HOTAIR represssed by GapmeR or treated with nonsilencing control, and hTERT-immortalized hMSCs with expression of control GFP, HOTAIR, or HOTAIR and EWS-FLI1, was used for gene expression analysis. Results: Defined gene expression signatures were defined as driven by HOTAIR in each cell line model, with a consensus set of gene identified in the Ewing sarcoma cell lines. Additionally, a set of genes regulated by HOTAIR independently of EWS-FLI1 was identified in the hTERT-hMSC models. Conclusions: HOTAIR expression regulates a set of genes critical to viability, cell adhesion, cell motility, and other markers of EMT and metastasis in Ewing sarcoma, independently of EWS-FLI1.
2018-01-24 | GSE109483 | GEO
Project description:To get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells. A673 and SK-N-MC Ewing sarcoma cells were transfected with specific siRNAs directed against EGR2 or EWSR1-FLI1 or non-targeting control siRNA. 48 h thereafter RNA was harvested and processed for microarray analysis.
2015-07-26 | E-GEOD-62090 | biostudies-arrayexpress
Project description:Identification of genes and pathways altered by PlaB, a bacterial natural product that acts as a spliceosome modulator by targeting the SF3b subunit of the spliceosome SKNMC, TC32, TC71, and RD-ES Ewing sarcoma cell lines were treated with 0.1% (v/v) DMSO vehicle or 5nM PlaB for 24 hours. Three samples in each group were analyzed.
2016-01-15 | E-GEOD-67548 | biostudies-arrayexpress
Project description:To get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells.
2015-07-26 | GSE62090 | GEO
Project description:Ewing sarcoma (EwS) is characterized by EWSR1-ETS fusion transcription factors converting polymorphic GGAA microsatellites (mSats) into potent neo-enhancers. Although the paucity of additional mutations makes EwS a genuine model to study principles of cooperation between dominant fusion oncogenes and neo-enhancers, this is impeded by the limited number of well-characterized models. Here we present the Ewing Sarcoma Cell Line Atlas (ESCLA), comprising whole-genome, DNA methylation, transcriptome, proteome, and chromatin immunoprecipitation sequencing (ChIP-seq) data of 18 cell lines with inducible EWSR1-ETS knockdown. The ESCLA shows hundreds of EWSR1-ETS-targets, the nature of EWSR1-ETS-preferred GGAA mSats, and putative indirect modes of EWSR1-ETS-mediated gene regulation, converging in the duality of a specific but plastic EwS signature. We identify heterogeneously regulated EWSR1-ETS-targets as potential prognostic EwS biomarkers. Our freely available ESCLA (http://r2platform.com/escla/) is a rich resource for EwS research and highlights the power of comprehensive datasets to unravel principles of heterogeneous gene regulation by chimeric transcription factors.
2024-06-18 | PXD052856 | Pride
Project description:Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta- catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic progression.
2018-02-07 | PXD007909 | Pride
Project description:HDGF ChIP-Seq in Ewing sarcoma cell line RD-ES
| PRJNA649791 | ENA