title: The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
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.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, B-9000 Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Boström
authors.forename: Francis
authors.initials: F
authors.lastname: Impens
authors.forename: Erik
authors.initials: E
authors.lastname: Fredlund
authors.forename: Gert
authors.initials: G
authors.lastname: Van Peer
authors.forename: Pasqualino
authors.initials: P
authors.lastname: De Antonellis
authors.forename: Kristoffer
authors.initials: K
authors.lastname: von Stedingk
authors.forename: Bart
authors.initials: B
authors.lastname: Ghesquière
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulte
authors.forename: Michael
authors.initials: M
authors.lastname: Dews
authors.forename: Andrei
authors.initials: A
authors.lastname: Thomas-Tikhonenko
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Massimo
authors.initials: M
authors.lastname: Zollo
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.forename: Håkan
authors.initials: H
authors.lastname: Axelson
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D035683:MicroRNAs; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta