EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors

被引：86

作者：

Avraham, Roi ^{[1
]}

Sas-Chen, Aldema ^{[1
]}

Manor, Ohad ^{[2
]}

Steinfeld, Israel ^{[3
]}

Shalgi, Reut ^{[4
]}

Tarcic, Gabi ^{[1
]}

Bossel, Noa ^{[5
]}

Zeisel, Amit ^{[5
]}

Amit, Ido ^{[6
]}

Zwang, Yaara ^{[1
]}

Enerly, Espen ^{[7
,8
]}

Russnes, Hege G. ^{[9
]}

Biagioni, Francesca ^{[10
]}

Mottolese, Marcella ^{[11
]}

Strano, Sabrina ^{[12
]}

Blandino, Giovanni ^{[10
]}

Borresen-Dale, Anne-Lise ^{[7
,8
]}

Pilpel, Yitzhak ^{[4
]}

Yakhini, Zohar ^{[3
,13
]}

Segal, Eran ^{[2
]}

Yarden, Yosef ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel

[3] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel

[4] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

[5] Weizmann Inst Sci, Dept Phys & Complex Syst, IL-76100 Rehovot, Israel

[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[7] Univ Oslo, Fac Med, NO-0317 Montebello, Norway

[8] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Genet, N-0027 Oslo, Norway

[9] Oslo Univ Hosp, Dept Pathol, N-0310 Oslo, Norway

[10] Regina Elena Inst Canc Res, Translat Oncogenom Unit, I-00128 Rome, Italy

[11] Regina Elena Inst Canc Res, Pathol Unit, I-00128 Rome, Italy

[12] Regina Elena Inst Canc Res, Mol Chemoprevent Grp, I-00128 Rome, Italy

[13] Agilent Labs, IL-49527 Tel Aviv, Israel

来源：

SCIENCE SIGNALING | 2010年 / 3卷 / 124期

关键词：

GENE-EXPRESSION; C-FOS; ROBUSTNESS; REGULATORS; PROTEINS; HOMOLOG; MODULE; SET;

D O I：

10.1126/scisignal.2000876

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：11

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