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NCOA3 upregulates MUC4 and MUC1 transcriptionally and through post-translational stability during pancreatic cancer development

ABSTRACT: Stable knock down of NCOA3 in PC cell lines resulted in significant downregulation of the two most differentially expressed MUCs in PC, MUC4 and MUC1. NCOA3 creates pro-inflammatory conditions by up-regulating chemokines like CXCL1, 2, 5 and CCL20

ORGANISM(S): Homo sapiens

PROVIDER: GSE51482 | GEO | 2013/12/19

SECONDARY ACCESSION(S): PRJNA223292

REPOSITORIES: GEO

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NCOA3 upregulates MUC4 and MUC1 transcriptionally and through post-translational stability during pancreatic cancer development

Project description:Stable knock down of NCOA3 in PC cell lines resulted in significant downregulation of the two most differentially expressed MUCs in PC, MUC4 and MUC1. NCOA3 creates pro-inflammatory conditions by up-regulating chemokines like CXCL1, 2, 5 and CCL20 Stable Knock down of NCOA3 in CD18/HPAF cell line. RNA was isolated from control and stably transfected cells. Each group has three biological replicate.

2013-12-19 | E-GEOD-51482 | biostudies-arrayexpress

NCOA3 upregulates MUC4 and MUC1 transcriptionally and through post-translational stability during pancreatic cancer development

Project description: Not available

| S-ECPF-GEOD-51482 | biostudies-other

MUC1-C Drives Lineage Plasticity in Progression to Neuroendocrine Prostate Cancer

Project description:Neuroendocrine prostate cancer (NEPC) is a highly aggressive malignancy of increasing prevalence with an unmet need for targeted therapeutic approaches. The oncogenic MUC1-C protein is overexpressed in castration-resistant prostate cancer (CRPC) and NEPC; however, there is no known role for MUC1-C in driving lineage plasticity to these advanced PC phenotypes. The present studies demonstrate that upregulation of MUC1-C in androgen-independent (AI) PC cells suppresses androgen receptor (AR) axis signaling and induces the neural BRN2 transcription factor by a previously unrecognized MYC-mediated mechanism. MUC1-C activates the BRN2 pathway in association with induction of MYCN, EZH2 and NE differentiation markers (ASCL1, AURKA and SYP), which are linked to NEPC progression. We also show that MUC1-C suppresses the p53 pathway, induces the Yamanaka pluripotency factors (OCT4, SOX2, KLF4 and MYC) and drives stemness. Of potential clinical relevance, targeting MUC1-C decreases PC self-renewal capacity and tumorigenicity, supporting the treatment of CRPC and NEPC with agents directed against this oncoprotein. These findings and the demonstration that MUC1-C is upregulated and associated with suppression of AR signaling, and increases in BRN2 expression and the NEPC score in PC tissues highlight the unanticipated importance of MUC1-C as a master effector of lineage plasticity in progression to advanced PC with NE features.

2019-12-02 | GSE139335 | GEO

Homo sapiens

Project description:NCOA3 upregulates MUC4 and MUC1 transcriptionally and through post-translational stability during pancreatic cancer development

| PRJNA223292 | ENA

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

Project description:Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery. Three biological replicates each for control scrambled shRNA and Ncoa3 shRNA transfected E14 mouse ESCs. The global gene expression profiles of Ncoa3 knockdown cells were compared to control scrambled shRNA knockdown cells 4 days post-transfection.

2012-10-02 | E-GEOD-40192 | biostudies-arrayexpress

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

2012-10-02 | GSE40192 | GEO

Sequencing the anti-MUC1 hybridoma antibody 139H2

Project description:Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at different mucosal surfaces including breast and intestine. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR can be powerful tools because of their multiplicity of binding and possible applications in the diagnosis and treatment of MUC1-expressing cancers. One such antibody is the hybridoma mouse monoclonal 139H2 which is also widely used as a research tool to study non-cancer MUC1. Here we report direct mass spectrometry-based sequencing of hybridoma-derived 139H2 IgG, which enabled reverse engineering of a recombinant 139H2.

2024-03-18 | PXD043489 | Pride

Expression of genes in the spleen of WT and MUC1.Tg mice immunized with dendritic cells loaded with MUC1 peptide

Project description:Goal of study: To determine differentially expressed genes with potential roles in tolerance and immunity in MUC1-immunized WT and MUC1.Tg mice WT (C57Bl/6) and MUC1.Tg mice were immunized (i.v.) with dendritic cells loaded with sythetic, human MUC1 peptide. At 24h and 72h splenic RNA from vaccination groups (n=3) was pooled and microarray performed.

2013-01-16 | E-GEOD-43503 | biostudies-arrayexpress

Regulation of the DNA damage response and melanoma susceptibility by NCOA3

Project description:NCOA3 has important roles in melanoma as a potential diagnostic and susceptibility marker, and as a target for therapy

2021-03-31 | GSE156062 | GEO

Ncoa3 in mouse embryonic stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE37262: A Nuclear Receptor Coactivator is Essential for Esrrb Activity and the Induction and Maintenance of the ES Cell State GSE40192: Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells Refer to individual Series

2012-10-02 | E-GEOD-40193 | biostudies-arrayexpress

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