Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SAGE-Seq gene expression profiles of Hs578T, MCF7, and SUM159PT cells treated with STAT3 or non-targeting siRNAs, DMSO, or CXCR2, PTGIS, HAS1, PFKFB3, JAK, or NQO1 inhibitor

ABSTRACT: To investigate potential links between Stat3 transcriptional activity and other signaling pathways in breast cancer, we determined the gene expression profiles of three breast cancer cell lines treated with JAK, PTGIS, PFKFB3, CXCR2, HAS1, or NQO1 inhibitor (all of which decreased Stat3 transcriptional activity in Hs 578T cells except for the NQO1 inhibitor), inhibitor treatment vehicle alone (DMSO), STAT3 siRNAs, or non-targeting siRNAs. Using the resulting data, we identified a gene signature that was significantly regulated by STAT3 siRNAs and similarly affected by the JAK and at least 3 other inhibitors (or by 4 other inhibitors) but not by the NQO1 inhibitor in Hs 578T cells that was enriched in genes involved in development and correlated with shorter distant metastasis-free survival in primary lymph-node-negative invasive breast tumors. These results emphasize the central importance of Stat3 in CD44+/CD24- stem-cell-like breast cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE22917 | GEO | 2011/09/08

SECONDARY ACCESSION(S): PRJNA127973

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

SAGE-Seq gene expression profiles of Hs578T, MCF7, and SUM159PT cells treated with STAT3 or non-targeting siRNAs, DMSO, or CXCR2, PTGIS, HAS1, PFKFB3, JAK, or NQO1 inhibitor

Project description:To investigate potential links between Stat3 transcriptional activity and other signaling pathways in breast cancer, we determined the gene expression profiles of three breast cancer cell lines treated with JAK, PTGIS, PFKFB3, CXCR2, HAS1, or NQO1 inhibitor (all of which decreased Stat3 transcriptional activity in Hs 578T cells except for the NQO1 inhibitor), inhibitor treatment vehicle alone (DMSO), STAT3 siRNAs, or non-targeting siRNAs. Using the resulting data, we identified a gene signature that was significantly regulated by STAT3 siRNAs and similarly affected by the JAK and at least 3 other inhibitors (or by 4 other inhibitors) but not by the NQO1 inhibitor in Hs 578T cells that was enriched in genes involved in development and correlated with shorter distant metastasis-free survival in primary lymph-node-negative invasive breast tumors. These results emphasize the central importance of Stat3 in CD44+/CD24- stem-cell-like breast cancer cells. This study includes SAGE-Seq libraries obtained using 27 samples that each underwent individual protocols. There are nine samples of each of three cell lines - Hs 578T, MCF7, and SUM159PT. The samples in each group were treated with either one of the six inhibitors, DMSO only (the background control for inhibitor-treated cells), STAT3 siRNAs, or non-targeting siRNAs (the background control for STAT3 siRNAs).

2011-09-08 | E-GEOD-22917 | biostudies-arrayexpress

Homo sapiens

Project description:SAGE-Seq gene expression profiles of Hs578T, MCF7, and SUM159PT cells treated with STAT3 or non-targeting siRNAs, DMSO, or CXCR2, PTGIS, HAS1, PFKFB3, JAK, or NQO1 inhibitor

| PRJNA127973 | ENA

NQO1 regulates inflammatory signaling

Project description:NQO1 silencing by a specific shRNA against NQO1 increased migration and hormone-independent survival in hormone-dependent human prostate cancer cells LNCaP. Genome wide array revealed that NQO1 blockade significantly upregulated pro-inflammatory mediators (e.g., IL-32, CCL2, IL-8, IL-17C, IL-10RA, CXCR2, CXCR7, NOS3) associated with prostate tumorigenesis. Two-condition experiment, control vs. NQO1 knockdown LNCaP cells. Biological replicates: 3 control replicates, 3 NQO1 knockdown replicates.

2014-08-26 | E-GEOD-58336 | biostudies-arrayexpress

NQO1 regulates inflammatory signaling

2014-08-26 | GSE58336 | GEO

Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation

Project description:NAD(P)H:quinone Oxidoreductase (NQO1) is essential for cell defense against reactive oxidative species, cancer, and metabolic stress. Recently, NQO1 was found in ribonucleoprotein (RNP) complexes, but NQO1-interacting mRNAs and the functional impact of such interactions are not known. Here, we used ribonucleoprotein immunoprecipitation (RIP) and microarray analysis to identify comprehensively the subset of NQO1 target mRNAs in human hepatoma HepG2 cells. One of its main targets, SERPINA1 mRNA, encodes the serine protease inhibitor α-1-antitrypsin, A1AT, which is associated with disorders including obesity-related metabolic inflammation, chronic obstructive pulmonary disease (COPD), liver cirrhosis and hepatocellular carcinoma. Biotin pulldown analysis indicated that NQO1 can bind the 3’ untranslated region (UTR) and the coding region (CR) of SERPINA1 mRNA. NQO1 did not affect SERPINA1 mRNA levels; instead, it enhanced the translation of SERPINA1 mRNA, as NQO1 silencing decreased the size of polysomes forming on SERPINA1 mRNA and lowered the abundance of A1AT. Luciferase reporter analysis further indicated that NQO1 regulates SERPINA1 mRNA translation through the SERPINA1 3’UTR. Accordingly, NQO1-KO mice had reduced hepatic and serum levels of A1AT and increased activity of neutrophil elastase, one of the main targets of A1AT. We propose that this novel mechanism of action of NQO1 as RNA-binding protein may help to explain its pleiotropic biological effects.

2017-05-22 | GSE81614 | GEO

NQO1 regulates expression and alternative splicing of apoptotic genes associated with Alzheimer's disease in PC-12 cells

Project description:Quinone oxidoreductase I (NQO1), an important antioxidant enzyme which plays an important role in monitoring cellular redox state, was altered in the brain tissues of Alzheimer’s disease (AD) patients. In addition to its traditional antioxidant effect, NQO1 is also a multifunctional RNA-binding protein (RBP) in post-transcriptional regulation. However, NQO1 in AD pathology by acting as an RBP is not studied. In the present study, the RBP functions of NQO1 in rat PC12 cells, a cell line widely used in neurological disease studies, were investigated using siRNA knock-down (KD) and following whole transcriptome (RNA-seq) analysis. Reduced levels of NQO1 led to a significant increase in cellular apoptosis, compared with control cells. Notably, RNA-seq analysis of the transcriptome of PC12 cells by NQO1-KD revealed that genes in certain apoptosis pathways, were under global transcriptional and alternative splicing regulation. Quantitative RT-PCR confirmed the NQO1-regulated transcription of apoptotic genes Cryab, Lgmn , Ngf, Apoe, Brd7, Stat3, and alternative splicing of Bin1, Picalm, Fyn. These NQO1-regulated genes have been found to be closely related to AD pathogenesis. Our findings suggest that NQO1 acts as an RBP and participates in the pathology of AD by regulating expression and alternative splicing of genes involved in apoptosis. The results of present study extend our understanding of the cellular and molecular mechanisms in AD pathogenesis, which might contribute to the development of novel therapeutic targets.

2023-10-20 | GSE185633 | GEO

Metabolic adaptations underlie epigenetic vulnerabilities in chemoresistant breast cancer. [RNA-Seq1]

Project description:Purpose:Assess the difference in gene expression of taxol-resistant TNBC cells relative to parental cells (MDA-MB-436 and HS 578T) upon treatment with UNC1999 3uM Conclusions: Our study identified genes significantly enriched or repressed in taxol-resistant cells relative to parental cells in both TNBC models (MDA_MB-436 and HS 578T)

2020-08-18 | GSE111920 | GEO

Interactome of menin in triple negative breast cancer cell line

Project description:The tumor suppressor menin has dual functions, acting either as a tumor suppressor or as an oncogene/oncoprotein, depending on the oncological context. Triple-negative breast cancer (TNBC) is characterized by lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and is often a basal-like breast cancer. TNBC is associated with a dismal prognosis and an insufficient response to chemotherapies. Previously, menin was shown to play a proliferative role in ER-positive breast cancer; however, functions of menin in TNBC remains unknown. We have demonstrated that menin is expressed in various TNBC subtypes with the strongest menin expression in the TNBC Hs 578T cells. Depletion of menin by antisense oligonucleotide inhibited cell proliferation, enhanced apoptosis, and induced cell cycle arrest in Hs 578T cells, highlighting oncogenic functions of menin in this TNBC model. To better understand the menin function, we performed AP-MS (Affinity Purification-Mass Spectrometry) using specific antibody against menin. Analysis of menin interactome suggested that menin could drive TNBC tumorigenesis through regulation of the MLL/KMT2A-driven transcriptional activity, mRNA 3’ end processing and apoptosis.

2021-09-10 | PXD024176 | Pride

JAK dependent survival of ALK- ALCL

Project description:Activating JAK and STAT mutations were discovered in many T-cell malignancies including ALK- anaplastic large cell lymphomas (ALCL). However, such mutations often occur in a minority of patients. To investigate the clinical application of targeting Janus Kinase (JAK) for ALK- ALCL, we treated ALK- cell lines of different histologic origins with JAK inhibitors. Interestingly, most exogenous cytokine independent cell lines responded to JAK inhibition regardless of JAK mutation status. JAK inhibitor sensitivity correlated with STAT3 phosphorylation status of tumor cells. Employing retroviral shRNA knockdown, we demonstrated that these JAK inhibitor sensitive cells were dependent on both JAK1 and STAT3 for survival. JAK1 and STAT3 gain-of-function mutations were found in some but not all JAK inhibitor sensitive cells. Moreover, the mutations alone could not explain the JAK1/STAT3 dependency as wild-type JAK1 or STAT3 was sufficient to promote cell survival in the cells that had either JAK1or STAT3 mutations. To investigate whether other mechanisms were involved, we knocked down upstream receptors GP130 or IL-2Rγ. Knockdown of GP130 or IL-2Rγ induced cell death in select JAK inhibitor sensitive cells. High levels of cytokine expression including IL-6 were demonstrated in cell lines as well as in primary ALK- ALCL tumors. Finally, ruxolitinib, a JAK1/2 inhibitor, was effective in vivo in a xenograft ALK- ALCL model. Our data suggest cytokine receptor signaling was required for tumor cell survival in diverse forms of ALK- ALCL even in the presence of JAK1/STAT3 mutations. Therefore, JAK-inhibitor therapy might benefit patients with ALK- ALCL that are pSTAT3+.

2017-08-22 | GSE96048 | GEO