期刊
MOLECULAR CELL
卷 40, 期 5, 页码 762-773出版社
CELL PRESS
DOI: 10.1016/j.molcel.2010.11.038
关键词
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资金
- Fund for Scientific Research [G.0198.08, 31511809]
- Belgian Kid's Fund
- Stichting tegen Kanker
- Ghent University [BOF 01D31406, BOF07/GOA/012]
- Swedish Childhood Cancer Foundation
- Swedish Cancer Society
- Royal Swedish Physiographic Society
- American Cancer Society
- Fund for Scientific Research- Flanders (Belgium) [G.0077.06]
- Inter University Attraction Poles [IUAP06]
- NCI [R01 CA122334, P30 CA016520]
- Associazione Italians contro la lotta al Neuroblastoma Progetto Pensiero [HEALTH-F2-2008-201662]
- AIRC Tumori Pediatrici
- BOF [01D35609]
- GOA [01G01910]
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-beta signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-beta signaling cascade as well as direct inhibition of TGF-beta-responsive genes.
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