Journal article

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

Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder T, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg R ...see all

Nature Cell Biology (2010)

  • 409

    Readers

    Mendeley users who have this article in their library.
  • 768

    Citations

    Citations of this article.
Sign in to save reference

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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Li Ma

  • Jennifer Young

  • Harsha Prabhala

  • Elizabeth Pan

  • Pieter Mestdagh

  • Daniel Muth

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free