The miR-17-92 MicroRNA Cluster regulates multiple components of the TGF-beta Pathway in neuroblastoma

The miR-17-92 MicroRNA Cluster regulates multiple components of the TGF-beta Pathway in neuroblastoma

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 rev...

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Hauptverfasser: Mestdagh, Pieter, Bostrom, Anna-Karin, Impens, Francis, Fredlund, Erik, Van Peer, Gert, De Antonellis, Pasqualino, von Stedingk, Kristoffer, Ghesquière, Bart, Schulte, Stefanie, Dews, Michael, Thomas-Tikhonenko, Andrei, Schulte, Johannes H, Zollo, Massimo, Schramm, Alexander, Gevaert, Kris, Axelson, Hakan, Speleman, Franki, Vandesompele, Jo
Format: Artikel
Sprache:eng
Schlagworte:
BIOGENESIS
Biology and Life Sciences
CANCER
EXPRESSION
GENE TARGETS
GROWTH
INDUCTION
MALIGNANT PHENOTYPE
NEURONAL DIFFERENTIATION
PROLIFERATION
PROTEOMICS
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Zusammenfassung: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.
ISSN:1097-2765