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

Open access
Ma, Li, Young, Jennifer, Prabhala, Harsha, Pan, Elizabeth, Mestdagh, Pieter, Muth, Daniel, Teruya-Feldstein, Julie, Reinhardt, Ferenc, Onder, Tamer T., Valastyan, Scott, Westermann, Frank, Speleman, Frank, Vandesompele, Jo, Weinberg, Robert A.·2010·Nature Cell Biology

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 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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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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CoChat. (2026). Citation check: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. https://app.cochat.ai/papers/10.1038/ncb2024
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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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.