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Sci. Signal., 1 June 2010
Vol. 3, Issue 124, p. ra43
[DOI: 10.1126/scisignal.2000876]

RESEARCH ARTICLES

EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors

Roi Avraham1, Aldema Sas-Chen1, Ohad Manor2, Israel Steinfeld3, Reut Shalgi4*, Gabi Tarcic1, Noa Bossel5, Amit Zeisel5, Ido Amit6, Yaara Zwang1, Espen Enerly7, Hege G. Russnes8, Francesca Biagioni9, Marcella Mottolese10, Sabrina Strano11, Giovanni Blandino9, Anne-Lise Børresen-Dale7, Yitzhak Pilpel4, Zohar Yakhini3,12, Eran Segal2, and Yosef Yarden1{dagger}

1 Department of Biological Regulation, Weizmann Institute of Science, 76100 Rehovot, Israel.
2 Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 76100 Rehovot, Israel.
3 Department of Computer Sciences, Technion–Israel Institute of Technology, 32000 Haifa, Israel.
4 Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
5 Department of Physics of Complex Systems, Weizmann Institute of Science, 76100 Rehovot, Israel.
6 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
7 Faculty of Medicine, University of Oslo, Montebello NO-0317, and Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0027 Oslo, Norway.
8 Department of Pathology, Oslo University Hospital, N-0310 Oslo, Norway.
9 Translational Oncogenomic Unit, Regina Elena Cancer Institute, 00128 Rome, Italy.
10 Pathology Unit, Regina Elena Cancer Institute, 00128 Rome, Italy.
11 Molecular Chemoprevention Group, Regina Elena Cancer Institute, 00128 Rome, Italy.
12 Agilent Laboratories, 49527 Tel Aviv, Israel.

* Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Abstract: Epidermal growth factor (EGF) stimulates cells by launching gene expression programs that are frequently deregulated in cancer. MicroRNAs, which attenuate gene expression by binding complementary regions in messenger RNAs, are broadly implicated in cancer. Using genome-wide approaches, we showed that EGF stimulation initiates a coordinated transcriptional program of microRNAs and transcription factors. The earliest event involved a decrease in the abundance of a subset of 23 microRNAs. This step permitted rapid induction of oncogenic transcription factors, such as c-FOS, encoded by immediate early genes. In line with roles as suppressors of EGF receptor (EGFR) signaling, we report that the abundance of this early subset of microRNAs is decreased in breast and in brain tumors driven by the EGFR or the closely related HER2. These findings identify specific microRNAs as attenuators of growth factor signaling and oncogenesis.

{dagger} To whom correspondence should be addressed. E-mail: yosef.yarden{at}weizmann.ac.il

Citation: R. Avraham, A. Sas-Chen, O. Manor, I. Steinfeld, R. Shalgi, G. Tarcic, N. Bossel, A. Zeisel, I. Amit, Y. Zwang, E. Enerly, H. G. Russnes, F. Biagioni, M. Mottolese, S. Strano, G. Blandino, A.-L. Børresen-Dale, Y. Pilpel, Z. Yakhini, E. Segal, Y. Yarden, EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors. Sci. Signal. 3, ra43 (2010).

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