Sign up & Download
Sign in

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

by Li Ma, Jennifer Young, Harsha Prabhala, Elizabeth Pan, Pieter Mestdagh, Daniel Muth, Julie Teruya-Feldstein, Ferenc Reinhardt, Tamer T Onder, Scott Valastyan, Frank Westermann, Frank Speleman, Jo Vandesompele, Robert A Weinberg show all authors
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 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.

Cite this document (BETA)

Authors on Mendeley

Readership Statistics

272 Readers on Mendeley
by Discipline
 
 
 
by Academic Status
 
37% Ph.D. Student
 
13% Post Doc
 
10% Student (Master)
by Country
 
3% United States
 
1% Belgium
 
1% United Kingdom

Sign up today - FREE

Mendeley saves you time finding and organizing research. Learn more

  • All your research in one place
  • Add and import papers easily
  • Access it anywhere, anytime

Start using Mendeley in seconds!

Already have an account? Sign in