The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis
Open accessAbstract
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 β-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.
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Cited by
Molecular mechanisms of epithelial–mesenchymal transition
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Non-coding RNAs in human disease
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Metadata
- Authors
- Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., Teruya-Feldstein, J., Reinhardt, F., Onder, T. T., Valastyan, S., Westermann, F., Speleman, F., Vandesompele, J., & Weinberg, R. A.
- Venue
- Nature Cell Biology
- Published
- 2010-02-21
- Volume
- 12
- Issue
- 3
- Pages
- 247-256
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2056302937
- Cited by
- 1,336
- References
- 13
- FWCI
- 34.86
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., Teruya-Feldstein, J., Reinhardt, F., Onder, T. T., Valastyan, S., Westermann, F., Speleman, F., Vandesompele, J., & Weinberg, R. A. (2010). miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biology. https://doi.org/10.1038/ncb2024
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