A MicroRNA Targeting Dicer for Metastasis Control

作者：Martello Graziano; Rosato Antonio; Ferrari Francesco; Manfrin Andrea; Cordenonsi Michelangelo; Dupont Sirio; Enzo Elena; Guzzardo Vincenza; Rondina Maria; Spruce Thomas; Parenti Anna R; Daidone Maria Grazia; Bicciato Silvio; Piccolo Stefano^*

来源：Cell, 2010, 141(7): 1195-U176.

DOI：10.1016/j.cell.2010.05.017

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.

• 出版日期2010-6-25