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
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma / 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.. - In: MOLECULAR CELL. - ISSN 1097-2765. - ELETTRONICO. - (2011), pp. 762-773. [10.1016/j.molcel.2010.11.038]
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
De Antonellis P;ZOLLO, MASSIMO;
2011
Abstract
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 genesI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
