EVI1 and AP1 Interact to Transcriptionally Regulate a Feed-Forward Loop Important for Cancer Cell Proliferation and Adhesion
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Justin Joseph Gnanakkan
PROVIDER: E-GEOD-25213 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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: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:Discovery of Evi1 genomic occupancy and target genes ChIP-enriched DNA and input DNA were analyzed by Solexa sequencing.
2012-01-15 | E-GEOD-25210 | biostudies-arrayexpress
Project description:Discovery of Evi1Δ324 genomic occupancy and target genes ChIP-enriched DNA and input DNA were analyzed by Solexa sequencing.
2013-02-28 | E-GEOD-42354 | biostudies-arrayexpress
Project description:We intraperitoneally injected SKOV3 (derived from human ovarian adenocarcinoma) expressing soluble fragment of human EP2 receptor or hIgG Fc (SKOV/ip-FuEP2/Ex2 and (SKOV/ip-Fumock). After 4 week, resulted tumors were lysed and total RNAs were isolated. By using microarray, We analyzed gene expression and identified distinct classes of up-regulated genes in SKOV/ip-FuEP2/Ex2-derived tumor. Tumor tissues from SKOV/ip-Fumock or SKOV/ip-FuEP2/Ex2 were lysed and total RNAs were extracted. And then we analyzed expression status by Affymetrix microarrays.
2012-06-21 | E-GEOD-38843 | biostudies-arrayexpress
Project description:Murine hematopoietic stem cells were sorted by FACS from C57BL/6 Evi1+/GFP mice. Gene expression profiles of LSKCD41–CD48–CD150+CD34+ cells, LSKCD41–CD48–CD150+CD34–Evi1-GFP– cells, and LSKCD41–CD48–CD150+CD34–Evi1-GFP+ cells were generated.
2020-11-27 | E-MTAB-7321 | biostudies-arrayexpress
Project description:A microarray analysis was performed to compare the global gene expression profile between C-CPE treated- and untreated- SKOV-3 ovarian cancer cells. SKOV-3 cells were treated with or without C-CPE for 72 hours, and total RNA was extracted and microarray was perfomed to compare the gene profiling changes between C-CPE treated- and untreated- cells. The experiment was performed in triplicate.
2010-06-23 | E-GEOD-22421 | biostudies-arrayexpress
Project description:Evi1 is essential for proliferation of hematopoietic stem cells and implicated in the development of myeloid disorders. Particularly, high Evi1 expression defines one of the largest clusters in acute myeloid leukemia and is significantly associated with extremely poor prognosis. Improvement of the therapeutic outcome of leukemia with activated Evi1 is one of the most challenging issues. However, mechanistic basis of Evi1-mediated leukemogenesis has not been fully elucidated. Here we show that Evi1 directly represses PTEN transcription in the murine bone marrow, which leads to activation of AKT/mTOR signaling. In a murine bone marrow transplantation model, Evi1 leukemia showed remarkable sensitivity to an mTOR inihibitor rapamycin. Furthermore, we found that Evi1 binds to several polycomb group proteins and recruits polycomb repressive complexes for PTEN downregulation, which reveals a novel epigenetic mechanism of AKT/mTOR activation in leukemia. Expression analyses and chromatin immunoprecipitation assays using human samples indicate that our findings in mice models are recapitulated in human leukemic cells. Dependence of Evi1-expressing leukemic cells on AKT/mTOR signaling provides the first example of targeted therapeutic modalities that suppress the leukemogenic activity of Evi1. The PTEN/AKT/mTOR signaling pathway and the Evi1-polycomb interaction can be promising therapeutic targets for leukemia with activated Evi1. Gene expression analysis for the purpose of identifying the target genes of Evi1 in primary bone marrow. 5-FU-primed mononuclear bone marrow cells harvested from C57/B6 mice were retrovirally transduced with Evi1-GFP or GFP. GFP positive cells were sorted and analyzed by Affymetrix® Mouse Genome 430 2.0 Array® for gene expression. Four independent experiments were performed.
2010-07-08 | E-GEOD-22434 | biostudies-arrayexpress
Project description:The EVI1 gene codes for a transcription factor with important roles in development and leukemogenesis. Overexpression of EVI1 in acute myeloid leukemia (AML) is one of the worst prognostic factors in patients with and without 3q26 rearrangements. Evi1 acts in several pathways through the interaction with proteins with important functions in hematopoiesis; however, the role of Evi1 as a transcription factor is not well known, and only some Evi1 target genes have been identified in mice. Our aim was to investigate the pathways and direct target genes of EVI1. Differential expression profiles after EVI1 knockdown allowed us to identify 125 genes involved in cell growth, differentiation and signal transduction that could be related to EVI1. Moreover, we looked for potential EVI1 binding sites within the region 1000 bp upstream of the transcription start sites of all human genes. We selected a total of 70 genes from the bioinformatics search, genes related to EVI1 by literature, and genes differentially expressed in the expression array. ChIP in the TF1 and HEL cell lines with two EVI1 antibodies demonstrated that EVI1 binds to the proximal promoter regions of 18 of these genes, most of them involved in important differentiation and proliferation pathways, confirming the important role of EVI1. Interestingly, EVI1 binds to the proximal region of its promoter, suggesting that it could be regulating its own transcription. Further functional studies are in progress. These data provide a starting point for further studies aimed at uncovering the mechanism for EVI1-induced transformation leukemias. Keywords: Gene expression analysis after transient knockdown of EVI1. 12 samples. Three replicates per experimental condition. Two cell lines (HTB-58, TF-1). Transient EVI1 knockdown using anti-EVI1 siRNA molecules vs. control siRNA.
2012-09-30 | E-GEOD-16238 | biostudies-arrayexpress