Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA123133 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE15193: IFN-alpha Stimulated Gene Expression in Sensitive and Resistant Renal Cell Carcinoma Cell Lines GSE16196: Differential IFNa-stimulated gene expression profiles in PLZF-inducible U937T monocyte cells Refer to individual Series
2010-05-18 | E-GEOD-16197 | biostudies-arrayexpress
Project description:Sensitivity to Interferon (IFN) is determined by a complex coordination of genetic and environmental factors. A previous experiment using two renal cancer cell lines differing markedly in their response to IFN were analyzed for their ISG profiles in order to determine gene expression changes associated with IFN sensitivity (Holko M, Williams BR. Functional annotation of IFN-alpha-stimulated gene expression profiles from sensitive and resistant renal cell carcinoma cell lines. J Interferon Cytokine Res 2006 Aug;26(8):534-47). Higher and more persistent expression of a subset of ISGs was noted in the IFN-sensitive RCC1 cells when compared with the relatively IFN-insensitive ACHN cells. A subset of Interferon stimulated genes (ISGs) whose sustained expression correlates with heightened IFN sensitivity were analyzed for functional and sequence similarities. This subset predominately contains genes involved in transcription, and most were found to contain in their promoters binding sites for promyleocytic zinc finger factor (PLZF), a transcriptional repressor identified by virtue of its role in the etiology of Acute Promyelocytic Leukemia (APL). Analysis of gene expression in a lymphoid cell line with inducible PLZF expression reveals that increased expression of immune system related genes including ISGs, depends on PLZF expression. Chromatin Immunoprecipitation assays show direct association between PLZF and in silico identified PLZF binding sites in ISG promoters. This study reveals a novel interaction between PLZF and IFN signaling.
2009-05-22 | GSE16196 | GEO
Project description:Sensitivity to Interferon (IFN) is determined by a complex coordination of genetic and environmental factors. A previous experiment using two renal cancer cell lines differing markedly in their response to IFN were analyzed for their ISG profiles in order to determine gene expression changes associated with IFN sensitivity (Holko M, Williams BR. Functional annotation of IFN-alpha-stimulated gene expression profiles from sensitive and resistant renal cell carcinoma cell lines. J Interferon Cytokine Res 2006 Aug;26(8):534-47). Higher and more persistent expression of a subset of ISGs was noted in the IFN-sensitive RCC1 cells when compared with the relatively IFN-insensitive ACHN cells. A subset of Interferon stimulated genes (ISGs) whose sustained expression correlates with heightened IFN sensitivity were analyzed for functional and sequence similarities. This subset predominately contains genes involved in transcription, and most were found to contain in their promoters binding sites for promyleocytic zinc finger factor (PLZF), a transcriptional repressor identified by virtue of its role in the etiology of Acute Promyelocytic Leukemia (APL). Analysis of gene expression in a lymphoid cell line with inducible PLZF expression reveals that increased expression of immune system related genes including ISGs, depends on PLZF expression. Chromatin Immunoprecipitation assays show direct association between PLZF and in silico identified PLZF binding sites in ISG promoters. This study reveals a novel interaction between PLZF and IFN signaling. A time course of IFNa treatment (0, 6, 16, 24 hrs) was performed in tetetracycline induced PLZF overexpressing and control U937T:PLZF45 cells. For the 0 hr time point, PLZF overexpression (Cy5) was compared with control cells (Cy3). For the 6, 16, and 24 hr IFN treated time points, treated RNA was labelled with Cy5 and non-IFN treated RNA with Cy3. Each IFN treatment time point was performed on control and PLZF-overexpressing cells respectively.
2010-05-18 | E-GEOD-16196 | biostudies-arrayexpress
Project description:The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness. Two human renal cell carcinoma cell lines (ACHN and RCC1) were treated with IFN-alpha for 3, 6, 9, 12, 16, and 24 hours. Total RNA from treated cells (Cy5) is hybridized with total RNA from untreated control cells (Cy3) to the custom ISG 1.3.1 cDNA array.
2010-05-18 | E-GEOD-15193 | biostudies-arrayexpress
Project description:A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. Foser et al. 2006 have shown that costimulation with IFN-alpa and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. Gene induction by small concentration of interferon-alpha-2a (100 U/ml) was analyzed in human cancer cell lines with differences in sensitivity to IFN-alpha and TGF-beta. Among other antiproliferative genes we found upregulated IFITM3 gene expression levels and inducibility of this antiproliferative protein in interferon sensitive cell lines.
2010-05-16 | GSE21158 | GEO
Project description:Clinical applications of human interferon (IFN)-alpha have met with varying degrees of success. Nevertheless, key molecules in IFN-alpha-induced cell death have not been clearly identified. Our previous study indicated that IFN (alpha, beta and omega) receptor (IFNAR) 1/2- and IFN regulatory factor (IRF) 9-RNA interference (RNAi) completely inhibited the antiproliferative (AP) activity of IFN-alpha in human ovarian adenocarcinoma OVCAR3 cells sensitive to IFN-alpha., followed by transcription of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, IFNAR1/2- and IRF9-RNAi inhibited the gene expression of TRAIL, but not of Fas ligand (FasL), following IFN-alpha treatment. In fact, TRAIL but not FasL inhibited the proliferation of OVCAR3 cells. IFN-alpha notably up-regulated the levels of TRAIL protein in the supernatant and on the membrane of OVCAR3 cells. Following TRAIL signaling, Caspase 8 inhibitor and BH3 interacting domain death agonist (BID)-RNAi significantly abrogated both AP activities of IFN-alpha and TRAIL. Furthermore, BID-RNAi prevented both IFN-alpha and TRAIL from collapsing the mitochondrial membrane potential (Delta Psi m). Finally, we provide important new evidence that BID overexpression led to a major enhancement of both AP activities of IFN-alpha and TRAIL in human lung carcinoma A549 cells resistant to IFN-alpha. Thus, this study suggests that BID is crucial in IFN-alpha-induced cell death, indicating a notable potential to be a targeted therapy for IFN-alpha resistant tumors. Biological replicate samples were created by treating OVCAR3 cells with IFN-alpha2c (n=8); IFNAR1-RNAi and IFN-alpha2c (n=4); IFNAR2-RNAi and IFN-alpha2c (n=5); ISGF3gamma-RNAi and IFN-alpha2c (n=3); and Negative RNAi and IFN-alpha2c (n=3). For analysis, the eight IFN-alpha2c treated OVCAR3 samples were paired with an untreated OVCAR3 control sample. The 15 RNAi treated OVCAR3 samples were paired with a Negative RNAi control sample.
2012-05-21 | E-GEOD-29790 | biostudies-arrayexpress
Project description:Clinical applications of human interferon (IFN)-alpha have met with varying degrees of success. Nevertheless, key molecules in IFN-alpha-induced cell death have not been clearly identified. Our previous study indicated that IFN (alpha, beta and omega) receptor (IFNAR) 1/2- and IFN regulatory factor (IRF) 9-RNA interference (RNAi) completely inhibited the antiproliferative (AP) activity of IFN-alpha in human ovarian adenocarcinoma OVCAR3 cells sensitive to IFN-alpha., followed by transcription of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, IFNAR1/2- and IRF9-RNAi inhibited the gene expression of TRAIL, but not of Fas ligand (FasL), following IFN-alpha treatment. In fact, TRAIL but not FasL inhibited the proliferation of OVCAR3 cells. IFN-alpha notably up-regulated the levels of TRAIL protein in the supernatant and on the membrane of OVCAR3 cells. Following TRAIL signaling, Caspase 8 inhibitor and BH3 interacting domain death agonist (BID)-RNAi significantly abrogated both AP activities of IFN-alpha and TRAIL. Furthermore, BID-RNAi prevented both IFN-alpha and TRAIL from collapsing the mitochondrial membrane potential (Delta Psi m). Finally, we provide important new evidence that BID overexpression led to a major enhancement of both AP activities of IFN-alpha and TRAIL in human lung carcinoma A549 cells resistant to IFN-alpha. Thus, this study suggests that BID is crucial in IFN-alpha-induced cell death, indicating a notable potential to be a targeted therapy for IFN-alpha resistant tumors.
2012-05-22 | GSE29790 | GEO
Project description:Plasmacytoid dendritic cells (pDCs) play a key role in the activation of the autoimmune response in LN. Recently we demonstrated that these cells infiltrate the kidney of patients with LN at tubulointerstitial level. The pDCs are the main producers of IFN-alpha, whose effects on the renal tubule are poorly understood. The aim of the study was to investigate the effects of INF-alpha in renal epithelial cells (RPTEC). We investigated the effect of IFN-alpha on the whole-genome gene expression profile in RPTEC cells,. Genomic analysis showed that after stimulation, 108 genes are up-regulated and only 7 are down-regulated, with a fold-change> 2. The Gene Set Enrichment analysis confirmed that IFN-alpha induced the pathway of antigen presentation and the inflammatory signaling in RPTEC. Among the up-regulated genes involved in these pathways, there were HLA-I, the ubiquitins (FBXO6 and DTX3L) and the immunoproteasome subunits LMP7. We performed the validation of these genes by real time PCR and citometry experiments on RPTEC stimulated with IFN-alpha. Immunohistochemical analysis of LMP7 and MXA protein, specific marker of IFN-alpha, showed a significant upregulatation of both proteins in renal biopsies of patients with LN class IV compared to class I. Confocal microscopy showed the colocalization of LMP7-MXA in tubular epithelium of patients with LN class IV and activation of inflammatory signaling via NF-kB in the MXA+ tubules. Our data suggested that inhibition of INF-alpha pathways could represent a novel therapeutic strategy to reduce renal tubular damage in patients with LN. To identify genes specifically modulated by INF-alpha in RPTEC, we stimulated 3 different cell clones with 100U/ml INF-alpha for 48 hours and compared their whole-genome gene expression profiles with that from 3 RPTEC clones cultured without stimuli.
2015-12-15 | E-GEOD-48551 | biostudies-arrayexpress
Project description:Molecular profiling of ovarian carcinoma platinum-sensitive and -resistant cell lines (microRNAs)
| PRJNA252705 | ENA
Project description:The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness.
2009-05-22 | GSE15193 | GEO