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The miR-17-92 MicroRNA Cluster Regulates Multiple Components of the TGF-beta Pathway in Neuroblastoma

Author:
  • Pieter Mestdagh
  • Anna-Karin Boström
  • Francis Impens
  • Erik Fredlund
  • Gert Van Peer
  • Pasqualino De Antonellis
  • Kristoffer von Stedingk
  • Bart Ghesquiere
  • Stefanie Schulte
  • Michael Dews
  • Andrei Thomas-Tikhonenko
  • Johannes H. Schulte
  • Massimo Zollo
  • Alexander Schramm
  • Kris Gevaert
  • Håkan Axelson
  • Frank Speleman
  • Jo Vandesompele
Publishing year: 2010
Language: English
Pages: 762-773
Publication/Series: Molecular Cell
Volume: 40
Issue: 5
Document type: Journal article
Publisher: Cell Press

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • Kidney cancer research group
  • ISSN: 1097-4164
Håkan Axelson
E-mail: hakan.axelson [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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