title: A MicroRNA targeting dicer for metastasis control.
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.
authors.affiliation: Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Martello
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrari
authors.forename: Andrea
authors.initials: A
authors.lastname: Manfrin
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cordenonsi
authors.forename: Sirio
authors.initials: S
authors.lastname: Dupont
authors.forename: Elena
authors.initials: E
authors.lastname: Enzo
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.forename: Maria
authors.initials: M
authors.lastname: Rondina
authors.forename: Thomas
authors.initials: T
authors.lastname: Spruce
authors.forename: Anna R
authors.initials: AR
authors.lastname: Parenti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Stefano
authors.initials: S
authors.lastname: Piccolo
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D043244:Ribonuclease III