[HTML][HTML] A MicroRNA targeting dicer for metastasis control

G Martello, A Rosato, F Ferrari, A Manfrin… - Cell, 2010 - cell.com
G Martello, A Rosato, F Ferrari, A Manfrin, M Cordenonsi, S Dupont, E Enzo, V Guzzardo…
Cell, 2010cell.com
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 …
Summary
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.
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