A MicroRNA Targeting Dicer for Metastasis Control

نویسندگان

  • Graziano Martello
  • Antonio Rosato
  • Francesco Ferrari
  • Andrea Manfrin
  • Michelangelo Cordenonsi
  • Sirio Dupont
  • Elena Enzo
  • Vincenza Guzzardo
  • Maria Rondina
  • Thomas Spruce
  • Anna R. Parenti
  • Maria Grazia Daidone
  • Silvio Bicciato
  • Stefano Piccolo
چکیده

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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بررسی ارتباط بین پلیمورفیسم‌ ژنهای مجموعه پردازشی MicroRNA (RAN rs14035,DICER rs3742330) و سقط مکرر خودبخودی در شهر تهران

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عنوان ژورنال:
  • Cell

دوره 141  شماره 

صفحات  -

تاریخ انتشار 2010