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

(2010) NATURE CELL BIOLOGY. 12(3). p.247-U52
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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.
Keywords
INVASION, ADHESION, TUMOR ANGIOGENESIS, STEM-CELLS, N-MYC, C-MYC, EXPRESSION, MAMMARY EPITHELIAL-CELLS, MESENCHYMAL TRANSITION, HUMAN BREAST-CANCER

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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.
@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},
}

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