Effects of EVI1 mild expression in HeLa cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33724 | GEO | 2012/01/15
SECONDARY ACCESSION(S): PRJNA148447
REPOSITORIES: GEO
Similar Datasets
Project description:We studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1Δ324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. This study provides human genome-wide mapping and expression analyses for EVI1 that will be useful for the research community.
2012-11-14 | GSE42251 | GEO
Project description:We studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1?324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. This study provides human genome-wide mapping and expression analyses for EVI1 that will be useful for the research community. 12 samples were collected. Each condition was done in 4 replicates, collected 24 hours after transfection (for mild expression of EVI1 or EVI1?324). Transfections with Flag-expressing vector were used as controls.
2012-11-14 | E-GEOD-42251 | biostudies-arrayexpress
Project description:We studied the variations of mRNA amounts after Flag-EVI1 or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. Furthermore, this study provides human genome-wide mapping and downstream analyses for EVI1 that will be useful for the research community. 8 samples were collected. Each condition was done in 4 replicates, collected 24 hours after transfection (for mild expression of EVI1). Transfections with Flag-expressing vector were used as controls.
2012-01-15 | E-GEOD-33724 | biostudies-arrayexpress
Project description:We studied the variations of mRNA amounts after Evi1 knockdown or Flag-Evi1 overexpression in SKOV-3 cells. Despites Evi1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why Evi1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for Evi1 in human ovarian carcinoma cells. We identified numerous Evi1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and Evi1 that regulated proliferation and adhesion through a feed-forward loop. Furthermore, this study provides human genome-wide mapping and downstream analyses for Evi1 that will be useful for the research community.
2012-01-15 | GSE25212 | GEO
Project description:We studied the variations of mRNA amounts after Evi1 knockdown or Flag-Evi1 overexpression in SKOV-3 cells. Despites Evi1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why Evi1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for Evi1 in human ovarian carcinoma cells. We identified numerous Evi1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and Evi1 that regulated proliferation and adhesion through a feed-forward loop. Furthermore, this study provides human genome-wide mapping and downstream analyses for Evi1 that will be useful for the research community. 16 samples were collected. Each condition was done in 4 replicates, collected 65 hours after transfection. Transfections with control siRNA or Flag-expressing vector were used as controls.
2012-01-15 | E-GEOD-25212 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable with current chemotherapy regimens. Insight into the mechanism by which EVI1 drives myeloid transformation is needed to target EVI1 in those leukemias. Here we demonstrate recurrent interaction of CTBP1/2 with a unique PLDLS motif in EVI1, which is indispensable for leukemic transformation of 3q26/MECOM rearranged AML. A PLDLS competitor construct outcompetes EVI1 to CTBP1/2 binding and inhibits AML proliferation in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML using specific inhibitors directed to EVI1/CTBP1/2 interaction. Our findings have important implications for other tumour types with aberrant expression of EVI1 or other oncogenic transcription factors that also depend on CTBP1/2 interaction.
2024-05-21 | PXD048760 | Pride
Project description:Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable with current chemotherapy regimens. Insight into the mechanism by which EVI1 drives myeloid transformation is needed to target EVI1 in those leukemias. Here we demonstrate recurrent interaction of CTBP1/2 with a unique PLDLS motif in EVI1, which is indispensable for leukemic transformation of 3q26/MECOM rearranged AML. A PLDLS competitor construct outcompetes EVI1 to CTBP1/2 binding and inhibits AML proliferation in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML using specific inhibitors directed to EVI1/CTBP1/2 interaction. Our findings have important implications for other tumour types with aberrant expression of EVI1 or other oncogenic transcription factors that also depend on CTBP1/2 interaction.
2023-07-13 | PXD043333 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE25210: Genome-wide mapping of Flag-Evi1 in SKOV-3 ovarian carcinoma cells GSE25212: Effects of Evi1 knockdown and overexpression in SKOV-3 ovarian carcinoma cells GSE33724: Effects of EVI1 mild expression in HeLa cells Refer to individual Series
2012-01-15 | E-GEOD-25213 | biostudies-arrayexpress
Project description:Background: The transcription factor EVI1 regulates cellular proliferation, differentiation, and apoptosis, and contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. Methods: U937T_EVI1, a previously established human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to genome wide gene expression microarray analysis. qRT-PCR was used to confirm the regulation of MS4A3 by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and direct binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Experimental results were tested for statistical significance using ANOVA and Student's t-test (two-tailed). Results: Gene expression microarray analysis identified 27 unique genes that were up-regulated and 29 that were down-regulated in response to EVI1 induction in the human myeloid cell line, U937. The most strongly repressed gene was membrane-spanning-4-domains subfamily-A member-3 (MS4A3), and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model. Conclusions: Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness. Time course of 2 biological replicates, plus 2 control samples; 20 arrays in total
2015-08-30 | E-GEOD-60100 | biostudies-arrayexpress
Project description:Background: The transcription factor EVI1 regulates cellular proliferation, differentiation, and apoptosis, and contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. Methods: U937T_EVI1, a previously established human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to genome wide gene expression microarray analysis. qRT-PCR was used to confirm the regulation of MS4A3 by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and direct binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Experimental results were tested for statistical significance using ANOVA and Student's t-test (two-tailed). Results: Gene expression microarray analysis identified 27 unique genes that were up-regulated and 29 that were down-regulated in response to EVI1 induction in the human myeloid cell line, U937. The most strongly repressed gene was membrane-spanning-4-domains subfamily-A member-3 (MS4A3), and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model. Conclusions: Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
2015-08-30 | GSE60100 | GEO