RNA sequencing of CSN5 inhibition in prostate cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE173466 | GEO | 2022/08/17
REPOSITORIES: GEO
Similar Datasets
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. This SuperSeries is composed of the SubSeries listed below.
2008-01-18 | GSE9206 | GEO
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A strain or line experiment design type assays differences between multiple strains, cultivars, serovars, isolates, lines from organisms of a single species. Keywords: strain_or_line_design
2008-01-18 | GSE9205 | GEO
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. Keywords: genetic_modification_design
2008-01-18 | GSE9204 | GEO
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. This SuperSeries is composed of the following subset Series: GSE9204: Role of CSN5 in breast cancer (siRNA transfections) GSE9205: Role of CSN5 in breast cancer (array CGH) Refer to individual Series
2010-06-29 | E-GEOD-9206 | biostudies-arrayexpress
Project description:Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared to dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. We demonstrate that CSN5 knockdown by small interfering (si) RNA caused a block in cell proliferation and cell cycle progression, and induced apoptosis of HCC cells in vitro. The transcriptomic analysis of CSN5 knockdown signature by microarray showed that the anti-proliferative effect was driven by a common subset of molecular alterations including downregulation of CDK6 or ITGB1, which are involved in cell cycle regulation or tumor invasion and functionally interconnected with key oncogenic regulators such as TGFβ1 and MYC. Western blot assay showed that CSN5 depletion significantly increases the phosphorylation of Smad2/3 and decreases the expression of ITGB1, CDK6 and cyclin D1 proteins, restoring the tumor suppressive function of RB and thereby contributing to inhibition of cell cycle progression. In addition, CSN5 knockdown increased the expression of Bak but decreased the level of Bcl-2, subsequently leading to apoptosis through the activation of caspase-3. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid-particles (SNALP) significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 plays a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy. Huh7 and HepG2 cells were treated with CSN5 siRNA and negative control siRNA for 48 hours and subjected to Illumina microarray analysis. 4 replicates each.
2011-12-27 | E-GEOD-26485 | biostudies-arrayexpress
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. Computed
2010-06-29 | E-GEOD-9204 | biostudies-arrayexpress
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A strain or line experiment design type assays differences between multiple strains, cultivars, serovars, isolates, lines from organisms of a single species. Computed
2010-06-29 | E-GEOD-9205 | biostudies-arrayexpress
Project description:Transcriptional profiling of cotton ovule cells. Comparison of expression of genes in cultured ovules (-1 DPA) treated with or without phytohormones (5um IAA and 1um GA) and over a time-course from 0 to 12 hours.
2015-05-01 | GSE66251 | GEO
Project description:Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared to dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. We demonstrate that CSN5 knockdown by small interfering (si) RNA caused a block in cell proliferation and cell cycle progression, and induced apoptosis of HCC cells in vitro. The transcriptomic analysis of CSN5 knockdown signature by microarray showed that the anti-proliferative effect was driven by a common subset of molecular alterations including downregulation of CDK6 or ITGB1, which are involved in cell cycle regulation or tumor invasion and functionally interconnected with key oncogenic regulators such as TGFβ1 and MYC. Western blot assay showed that CSN5 depletion significantly increases the phosphorylation of Smad2/3 and decreases the expression of ITGB1, CDK6 and cyclin D1 proteins, restoring the tumor suppressive function of RB and thereby contributing to inhibition of cell cycle progression. In addition, CSN5 knockdown increased the expression of Bak but decreased the level of Bcl-2, subsequently leading to apoptosis through the activation of caspase-3. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid-particles (SNALP) significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 plays a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy.
2011-12-27 | GSE26485 | GEO
Project description:We performed RNA-seq analysis using different prostate cancer cell lines (PC3 and 22Rv1) after morusin treatment. We reported that morusin regulates Akt/mTOR pathway-associated genes in PC3 and 22Rv1 cells. Morusin induces apoptosis and suppresses cell cycle progression, cell migration and invasion in PC3 and 22Rv1 cells.
2024-08-18 | GSE211522 | GEO