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
PROVIDER: GSE25213 | GEO | 2012/01/15
SECONDARY ACCESSION(S): PRJNA134331
REPOSITORIES: GEO
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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
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Project description:Analysis of miRNA expression in human breast cancer samples with Agilent's miRNA arrays. These samples are part of a study where we have investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. We observed that indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Abstract of paper: Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. Indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these microRNAs silence anti-proliferative genes, which themselves are E2F1 targets. Thus, microRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative microRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Together these findings position microRNAs as novel key players in the mammalian cellular proliferation network. Keywords: Breast Cancer, miRNA, p53. 18 Primary human breast cancer samples analyzed for their miRNA expression. From two to four replicates were performed for each sample. Quality check (QC) were performed with Feature Extraction 9.1.3.44 and arrays not passing QC were excluded
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Project description:miRNA expression profiles of WI38 primary human fibroblasts with an active or inactive p53. Cells were compared under normal untreated conditions (young and proliferating cells), after DNA damage with Doxorubicin, and upon entry into replicative senescence. Keywords: miRNA, WI-38, p53, GSE56, Senescence, Doxorubicin, Cancer, DNA-damage, fibroblasts. 6 samples of WI38 cells were analyzed on 12 Exiqon miRcurry LNA arrays in biological duplicates (2 different cell culture plates for each experimental condition). The six conditions included: 1. [Con_Young] - Primary Young WI38 cells (passage 20) with a control retroviral vector (pLXSN-NEO). Untreated. 2. [GSE_Young] -Primary Young WI38 cells (passage 20) with a retroviral vector encoding for the p53-inactivating peptide GSE56 (pLXSN-NEO-GSE56).Untreated. 3. [Con_Dox] -Primary Young WI38 cells (passage 20) with a control retroviral vector (pLXSN-NEO). Treated with Doxorubicin (0.2 micrograms/ml) for 24 hours). 4. [GSE_Dox] Primary Young WI38 cells (passage 20) with a retroviral vector encoding for the p53-inactivating peptide GSE56 (pLXSN-NEO-GSE56). Treated with Doxorubicin (0.2 micrograms/ml) for 24 hours). 5. [Con_Old] - Sesescent WI38 cells (passage 30) with a control retroviral vector (pLXSN-NEO). Untreated. 6. [GSE_Old] - Senescent WI38 cells (passage 26) with a retroviral vector encoding for the p53-inactivating peptide GSE56 (pLXSN-NEO-GSE56).Untreated. RNA was extracted with TRI-Reagent and sent for labeling and hybridization in Exiqon laboratories (In Denamark). Samples were labeled with Cy5. Reference sample (Cy3) was an RNA mix of all samples. Log2 for Ratio(Cy5/Cy3) was used for further analysis.
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Project description:Analysis of miRNA expression in human breast cancer samples with Agilent's miRNA arrays. These samples are part of a study where we have investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. We observed that indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Abstract of paper: Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. Indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these microRNAs silence anti-proliferative genes, which themselves are E2F1 targets. Thus, microRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative microRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Together these findings position microRNAs as novel key players in the mammalian cellular proliferation network. Keywords: Breast Cancer, miRNA, p53. 18 Primary human breast cancer samples analyzed for their miRNA expression. From two to four replicates were performed for each sample. Quality check (QC) were performed with Feature Extraction 9.1.3.44 and arrays not passing QC were excluded
2008-09-22 | E-GEOD-12848 | biostudies-arrayexpress
Project description:Analysis of miRNA expression in human breast cancer samples with Agilent's miRNA arrays. These samples are part of a study where we have investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. We observed that indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Abstract of paper: Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. Indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these microRNAs silence anti-proliferative genes, which themselves are E2F1 targets. Thus, microRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative microRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Together these findings position microRNAs as novel key players in the mammalian cellular proliferation network. Keywords: Breast Cancer, miRNA, p53.
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Project description:There is a distinctive miRNA expression profile between early (young) and replicative senescence (old). We observed a cluster of miRNAs that were repressed upon senescence in both MRC-5 and WI-38 fibroblast cells.
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Project description:miRNA expression profiles of WI38 primary human fibroblasts with an active or inactive p53. Cells were compared under normal untreated conditions (young and proliferating cells), after DNA damage with Doxorubicin, and upon entry into replicative senescence. Keywords: miRNA, WI-38, p53, GSE56, Senescence, Doxorubicin, Cancer, DNA-damage, fibroblasts.
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