Microarray analysis of NNMT overexpression and knockdown in stromal cells
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ABSTRACT:
PROVIDER: PRJNA447980 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Analysis of gene expression in human CAFs with control (shCtrl) or shRNA against NNMT (shNNMT) expression or normal fibroblasts expressing control (Ctrl) or NNMT overexpression (NNMT) constructs. Cells were infected with lentivirus to express the indicated shRNA construct. Hypothesis is that knockdown of NNMT will affect expression of genes via regulation of histone methylation status.
2019-05-01 | GSE112497 | GEO
Project description:Genome-wide DNA methylation profiling in response to overexpression or knockdown of NNMT in stromal cells. The Illumina MethylationEPIC array was used to profiled genome-wide methylation of normal fibroblasts expressing a control construct or NNMT overexpression construt and cancer-associated fibroblasts (CAFs) expressing an shCtrl or shNNMT construct. Two biological replicates of each experimental group were profiled following growth in 10 micromolar methionine growth media for 21 days.
2019-05-01 | GSE126672 | GEO
Project description:DNA methylation analysis of NNMT overexpression and knockdown in stromal cells
| PRJNA522911 | ENA
Project description:Analysis of gene expression in human CAFs with control (shCtrl) or shRNA against NNMT (shNNMT) expression. Cells were infected with lentivirus to express the indicated shRNA construct. Hypothesis is that knockdown of NNMT will affect expression of genes via regulation of histone methylation status.
2022-05-01 | GSE98267 | GEO
Project description:High grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target.
2019-05-01 | GSE124014 | GEO
Project description:High grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target.
2019-05-01 | GSE124015 | GEO
Project description:High-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. We developed a label- free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene- expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.
2019-04-18 | PXD006396 | Pride
Project description:RNA sequencing of NNMT overexpression in 3T3 fibroblasts
| PRJNA510587 | ENA
Project description:FHL3 overexpression microarray
| PRJNA432519 | ENA