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

Mestdagh, Pieter; Boström, Anna-Karin LU ; Impens, Francis; Fredlund, Erik; Van Peer, Gert; De Antonellis, Pasqualino; von Stedingk, Kristoffer LU ; Ghesquiere, Bart; Schulte, Stefanie and Dews, Michael, et al. (2010) In Molecular Cell 40(5). p.762-773
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-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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Molecular Cell
volume
40
issue
5
pages
762 - 773
publisher
Cell Press
external identifiers
  • wos:000285405800010
  • scopus:78649941638
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.11.038
language
English
LU publication?
yes
id
9393d28d-67f9-4b43-8bfb-e84e229fbf83 (old id 1771167)
date added to LUP
2011-02-02 14:43:55
date last changed
2018-07-15 03:10:04
@article{9393d28d-67f9-4b43-8bfb-e84e229fbf83,
  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-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.},
  author       = {Mestdagh, Pieter and Boström, Anna-Karin and Impens, Francis and Fredlund, Erik and Van Peer, Gert and De Antonellis, Pasqualino and von Stedingk, Kristoffer and Ghesquiere, Bart and Schulte, Stefanie and Dews, Michael and Thomas-Tikhonenko, Andrei and Schulte, Johannes H. and Zollo, Massimo and Schramm, Alexander and Gevaert, Kris and Axelson, Håkan and Speleman, Frank and Vandesompele, Jo},
  issn         = {1097-4164},
  language     = {eng},
  number       = {5},
  pages        = {762--773},
  publisher    = {Cell Press},
  series       = {Molecular Cell},
  title        = {The miR-17-92 MicroRNA Cluster Regulates Multiple Components of the TGF-beta Pathway in Neuroblastoma},
  url          = {http://dx.doi.org/10.1016/j.molcel.2010.11.038},
  volume       = {40},
  year         = {2010},
}