Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA246047 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1267910.fastq.gz | Fastqsanger.gz |
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Project description:PRKCI regulates tumor microenvironment through YAP1 [Affymetrix]
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Project description:PRKCI regulates tumor microenvironment through YAP1
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Project description:A key feature of serous ovarian cancer is frequent amplification in the 3q26 locus, which harbors the PRKCI gene. Here we show that PRKCI is amplified and overexpressed in a 78% of high-grade serous ovarian carcinoma. Our in vivo studies with orthotopic mouse models establish it as an ovarian cancer oncogene. This oncogenic property of PRKCI is mediated by regulation of YAP1 activity. Accordingly YAP1 knockdown partially rescues PRKCI mediated tumorigenesis. Integrated gene expression profiling and YAP1 promoter occupancy analyses reveal that PRKCI and YAP1 cooperate to transcriptionally regulate genes affecting the tumor immune microenvironment. Consistently, CD11b+Gr1+Ly6G+ MDSCs are increased in the tumor microenvironment of PRKCI over-expressing tumors. Importantly, we show that elevated PRKCI expression in high-grade serous ovarian carcinomas strongly correlated with assignment to immunoreactive subtype. In summary, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immunosuppressive microenvironment in ovarian cancers.
2018-01-15 | GSE57257 | GEO
Project description:A key feature of serous ovarian cancer is frequent amplification in the 3q26 locus, which harbors the PRKCI gene. Here we show that PRKCI is amplified and overexpressed in a 78% of high-grade serous ovarian carcinoma. Our in vivo studies with orthotopic mouse models establish it as an ovarian cancer oncogene. This oncogenic property of PRKCI is mediated by regulation of YAP1 activity. Accordingly YAP1 knockdown partially rescues PRKCI mediated tumorigenesis. Integrated gene expression profiling and YAP1 promoter occupancy analyses reveal that PRKCI and YAP1 cooperate to transcriptionally regulate genes affecting the tumor immune microenvironment. Consistently, CD11b+Gr1+Ly6G+ MDSCs are increased in the tumor microenvironment of PRKCI over-expressing tumors. Importantly, we show that elevated PRKCI expression in high-grade serous ovarian carcinomas strongly correlated with assignment to immunoreactive subtype. In summary, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immunosuppressive microenvironment in ovarian cancers.
2018-01-15 | GSE57236 | GEO
Project description:A key feature of ovarian high-grade serous carcinoma is frequent amplification of the 3q26 locus. Here we show that PRKCI, located on the 3q26 locus is not only amplified and overexpressed in 78% of HGSC patient samples but is also expressed in early fallopian tube lesions, called Serous Tubal Intraepithelial Carcinoma. In vivo studies in a transgenic mouse model establish PRKCI as an ovarian cancer oncogene and identify YAP1 as a downstream regulator. Together, PRKCI and YAP1 regulate TNFα to promote an immune suppressive microenvironment and inhibit cytotoxic T-cell infiltration in tumors. High PRKCI expressing human ovarian tumors show decreased cytotoxic T-cell infiltration. Taken together, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immune microenvironment in ovarian cancer.
2018-06-01 | GSE57262 | GEO
Project description:A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-iota (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called Serous Tubal Intraepithelial Carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer specific oncogene and system level and functional analyses identify YAP1 as a downstream effector in tumor progression. Mechanistically, the oncogenic activity of the PRKCI-YAP1 axis relates in part to the upregulation of TNFα to promote an immune suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T cell infiltration. In human ovarian cancers, high PRKCI expression also correlates with high expression of YAP1 and low infiltration of cytotoxic T-cell. The PRKCI-YAP1 regulation of the tumor immunity provides a therapeutic strategy for highly lethal ovarian cancer. Robust multi-array average (RMA) method was used with default options (with background correction, quantile normalization, and log transformation) to normalize raw data from batches using R/Bioconductor‘s affy package
2018-06-01 | GSE82319 | GEO
Project description:PRKCI promotes immune suppression in ovarian tumors through YAP1
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Project description:PRKCI promotes immune suppression in ovarian cancer through YAP1
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Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO