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  • The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.

The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.

Molecular cell (2010-12-15)
Pieter Mestdagh, Anna-Karin Boström, Francis Impens, Erik Fredlund, Gert Van Peer, Pasqualino De Antonellis, Kristoffer von Stedingk, Bart Ghesquière, Stefanie Schulte, Michael Dews, Andrei Thomas-Tikhonenko, Johannes H Schulte, Massimo Zollo, Alexander Schramm, Kris Gevaert, Håkan Axelson, Frank Speleman, Jo Vandesompele
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 genes.

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MISSION® LightSwitch Luciferase Assay Reagent, Fully optimized reporter system