A microRNA targeting dicer for metastasis control

Graziano Martello, Antonio Rosato, Francesco Ferrari, Andrea Manfrin, Michelangelo Cordenonsi, Sirio Dupont, Elena Enzo, Vincenza Guzzardo, Maria Rondina, Thomas Spruce, Anna R. Parenti, Maria Grazia Daidone, Silvio Bicciato, Stefano Piccolo

Research output: Contribution to journalArticlepeer-review

Abstract

Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. Here we identify a microRNA family, miR-103/107, that attenuates miRNA biosynthesis by targeting Dicer, a key component of the miRNA processing machinery. In human breast cancer, high levels of miR-103/107 are associated with metastasis and poor outcome. Functionally, miR-103/107 confer migratory capacities in vitro and empower metastatic dissemination of otherwise nonaggressive cells in vivo. Inhibition of miR-103/107 opposes migration and metastasis of malignant cells. At the cellular level, a key event fostered by miR-103/107 is induction of epithelial-to-mesenchymal transition (EMT), attained by downregulating miR-200 levels. These findings suggest a new pathway by which Dicer inhibition drifts epithelial cancer toward a less-differentiated, mesenchymal fate to foster metastasis.

Original languageEnglish
Pages (from-to)1195-1207
Number of pages13
JournalCell
Volume141
Issue number7
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Humdisease
  • RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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