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

A MicroRNA targeting dicer for metastasis control / Martello, G; Rosato, A; Ferrari, F; Manfrin, A; Cordenonsi, M; Dupont, S; Enzo, Elena; Guzzardo, V; Rondina, M; Spruce, T; Parenti, Ar; Daidone, Mg; Bicciato, Silvio; Piccolo, S.. - In: CELL. - ISSN 0092-8674. - STAMPA. - 141:7(2010), pp. 1195-1207. [10.1016/j.cell.2010.05.017]

A MicroRNA targeting dicer for metastasis control

ENZO, ELENA;BICCIATO, Silvio;
2010

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
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A MicroRNA targeting dicer for metastasis control / Martello, G; Rosato, A; Ferrari, F; Manfrin, A; Cordenonsi, M; Dupont, S; Enzo, Elena; Guzzardo, V; Rondina, M; Spruce, T; Parenti, Ar; Daidone, Mg; Bicciato, Silvio; Piccolo, S.. - In: CELL. - ISSN 0092-8674. - STAMPA. - 141:7(2010), pp. 1195-1207. [10.1016/j.cell.2010.05.017]
Martello, G; Rosato, A; Ferrari, F; Manfrin, A; Cordenonsi, M; Dupont, S; Enzo, Elena; Guzzardo, V; Rondina, M; Spruce, T; Parenti, Ar; Daidone, Mg; Bicciato, Silvio; Piccolo, S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/645135
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