The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma
| Autor: | Bart Ghesquière, Kris Gevaert, Massimo Zollo, Francis Impens, Kristoffer von Stedingk, Pieter Mestdagh, Håkan Axelson, Gert Van Peer, Stefanie Schulte, Alexander Schramm, Franki Speleman, Pasqualino De Antonellis, Erik Fredlund, Andrei Thomas-Tikhonenko, Jo Vandesompele, Michael Dews, Johannes H. Schulte, Anna-Karin Boström |
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| Přispěvatelé: | Mestdagh, P, Boström, Ak, Impens, F, Fredlund, E, Van Peer, G, De Antonellis, P, von Stedingk, K, Ghesquière, B, Schulte, S, Dews, M, Thomas Tikhonenko, A, Schulte, Jh, Zollo, Massimo, Schramm, A, Gevaert, K, Axelson, H, Speleman, F, Vandesompele, J. |
| Rok vydání: | 2011 |
| Předmět: |
EXPRESSION
NEURONAL DIFFERENTIATION Upstream and downstream (transduction) BIOGENESIS Transplantation Heterologous Medizin Mice Nude Smad2 Protein Biology Article Cell Line Mice Neuroblastoma 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Transforming Growth Factor beta MALIGNANT PHENOTYPE Stable isotope labeling by amino acids in cell culture microRNA Cell Adhesion Animals Cell adhesion Molecular Biology Cell Proliferation 030304 developmental biology 0303 health sciences INDUCTION PROLIFERATION Biology and Life Sciences Cell Biology Transforming growth factor beta CANCER GENE TARGETS Cell biology MicroRNAs 030220 oncology & carcinogenesis Cancer cell biology.protein GROWTH PROTEOMICS |
| Zdroj: | Molecular Cell; Vol 40 MOLECULAR CELL |
| ISSN: | 1097-2765 |
| Popis: | 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-β signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-β signaling cascade as well as direct inhibition of TGF-β-responsive genes. |
| Databáze: | OpenAIRE |
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