EGF decreases the abundance of MicroRNAs that restrain oncogenic transcription factors

Roi Avraham, Aldema Sas-Chen, Ohad Manor, Israel Steinfeld, Reut Shalgi, Gabi Tarcic, Noa Bossel, Amit Zeisel, Ido Amit, Yaara Zwang, Espen Enerly, Hege G. Russnes, Francesca Biagioni, Marcella Mottolese, Sabrina Strano, Giovanni Blandino, Anne Lise Borresen-Dale, Yitzhak Pilpel, Zohar Yakhini, Eran SegalYosef Yarden

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalScience Signaling
Volume3
Issue number124
DOIs
Publication statusPublished - Jun 1 2010

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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