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miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis

L Ma, J Young, H Prabhala, E Pan, Pieter Mestdagh UGent, D Muth, J Teruya-Feldstein, F Reinhardt, TT Onder and S Valastyan, et al. (2010) NATURE CELL BIOLOGY. 12(3). p.247-U52
abstract
MicroRNAs (miRNAs) are increasingly implicated in regulating the malignant progression of cancer. Here we show that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness. miR-9-mediated E-cadherin downregulation results in the activation of beta-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a 'miRNA sponge' in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INVASION, ADHESION, TUMOR ANGIOGENESIS, STEM-CELLS, N-MYC, C-MYC, EXPRESSION, MAMMARY EPITHELIAL-CELLS, MESENCHYMAL TRANSITION, HUMAN BREAST-CANCER
journal title
NATURE CELL BIOLOGY
Nat. Cell Biol.
volume
12
issue
3
pages
25 pages
publisher
NATURE PUBLISHING GROUP
place of publication
LONDON
Web of Science type
Article
Web of Science id
000275054200010
JCR category
CELL BIOLOGY
JCR impact factor
19.407 (2010)
JCR rank
6/174 (2010)
JCR quartile
1 (2010)
ISSN
1465-7392
DOI
10.1038/ncb2024
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1004359
handle
http://hdl.handle.net/1854/LU-1004359
date created
2010-07-06 16:18:28
date last changed
2010-07-12 10:22:53
@article{1004359,
  abstract     = {MicroRNAs (miRNAs) are increasingly implicated in regulating the malignant progression of cancer. Here we show that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness. miR-9-mediated E-cadherin downregulation results in the activation of beta-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a 'miRNA sponge' in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin.},
  author       = {Ma, L and Young, J and Prabhala, H and Pan, E and Mestdagh, Pieter and Muth, D and Teruya-Feldstein, J and Reinhardt, F and Onder, TT and Valastyan, S and Westermann, F and Speleman, Franki and Vandesompele, Jo and Weinberg, RA},
  issn         = {1465-7392},
  journal      = {NATURE CELL BIOLOGY},
  keyword      = {INVASION,ADHESION,TUMOR ANGIOGENESIS,STEM-CELLS,N-MYC,C-MYC,EXPRESSION,MAMMARY EPITHELIAL-CELLS,MESENCHYMAL TRANSITION,HUMAN BREAST-CANCER},
  language     = {eng},
  number       = {3},
  pages        = {247--U52},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis},
  url          = {http://dx.doi.org/10.1038/ncb2024},
  volume       = {12},
  year         = {2010},
}

Chicago
Ma, L, J Young, H Prabhala, E Pan, Pieter Mestdagh, D Muth, J Teruya-Feldstein, et al. 2010. “miR-9, a MYC/MYCN-activated microRNA, Regulates E-cadherin and Cancer Metastasis.” Nature Cell Biology 12 (3): 247–U52.
APA
Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., Teruya-Feldstein, J., et al. (2010). miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. NATURE CELL BIOLOGY, 12(3), 247–U52.
Vancouver
1.
Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. NATURE CELL BIOLOGY. LONDON: NATURE PUBLISHING GROUP; 2010;12(3):247–U52.
MLA
Ma, L, J Young, H Prabhala, et al. “miR-9, a MYC/MYCN-activated microRNA, Regulates E-cadherin and Cancer Metastasis.” NATURE CELL BIOLOGY 12.3 (2010): 247–U52. Print.