Cell
Volume 141, Issue 7, 25 June 2010, Pages 1195-1207
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Article
A MicroRNA Targeting Dicer for Metastasis Control

https://doi.org/10.1016/j.cell.2010.05.017Get rights and content
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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.

Highlights

miR-103/107 is required and sufficient to inhibit Dicer and miRNA processing ► Expression of miR-103/107 correlates with poor prognosis in human breast cancer ► miR-103/107 impart metastatic proclivity to breast cancer cells ► miR-103/107-Dicer axis controls epithelial plasticity, in part via miR-200 regulation

RNA
HUMDISEASE

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