EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors.
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.
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Roi
R
Avraham
Aldema
A
Sas-Chen
Ohad
O
Manor
Israel
I
Steinfeld
Reut
R
Shalgi
Gabi
G
Tarcic
Noa
N
Bossel
Amit
A
Zeisel
Ido
I
Amit
Yaara
Y
Zwang
Espen
E
Enerly
Hege G
HG
Russnes
Francesca
F
Biagioni
Marcella
M
Mottolese
Sabrina
S
Strano
Giovanni
G
Blandino
Anne-Lise
AL
Børresen-Dale
Yitzhak
Y
Pilpel
Zohar
Z
Yakhini
Eran
E
Segal
Yosef
Y
Yarden
D001932:Brain Neoplasms / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D012334:RNA, Neoplasm; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors