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