A MicroRNA targeting dicer for metastasis control.
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.
Martello
Graziano
G
Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
Rosato
Antonio
A
Ferrari
Francesco
F
Manfrin
Andrea
A
Cordenonsi
Michelangelo
M
Dupont
Sirio
S
Enzo
Elena
E
Guzzardo
Vincenza
V
Rondina
Maria
M
Spruce
Thomas
T
Parenti
Anna R
AR
Daidone
Maria Grazia
MG
Bicciato
Silvio
S
Piccolo
Stefano
S
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*
D035683:MicroRNAs; D043244:Ribonuclease III