Transcriptomics

Dataset Information

7

P53-repressed miRNAs are Involved with E2F in a Feed Forward Loop Promoting Proliferation


ABSTRACT: 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

ORGANISM(S): Homo sapiens  

SUBMITTER: Giang Nguyen   Moshe Oren  Reut Shalgi  Yosef Buganim  Doron Ginsberg  Ran Brosh  Naomi Goldfinger  Katya Korotayev  Hilde Johnsen  Yitzhak Pilpel  Anne-Lise Børresen-Dale  Varda Rotter  Curtis C Harris  Gilad Landan  Ido Goldstein  Espen Enerly  Hilla Solomon  Shalom Madar  Atar Liran 

PROVIDER: E-GEOD-12848 | ArrayExpress | 2008-09-22

SECONDARY ACCESSION(S): GSE12848PRJNA111075

REPOSITORIES: GEO, ArrayExpress

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Publications


Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs (miRNAs) 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 transcriptional regulators, E2F and p53, their targets and a family of 15 miRNAs. Indicative of t  ...[more]

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