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Genes 2014, 5(3), 804-820; doi:10.3390/genes5030804

Functional Role of the microRNA-200 Family in Breast Morphogenesis and Neoplasia

1
Stem Cell Research Unit, Department of Medical Faculty, Biomedical Center, University of Iceland, Vatnsmyrarvegi 16, 101 Reykjavík, Iceland
2
Department of Laboratory Hematology, Landspitali University Hospital, Hringbraut, 101 Reykjavík, Iceland
3
Department of Pharmacology and Toxicology, Medical Faculty, University of Iceland, Hofsvallagotu 53, 107 Reykjavík, Iceland
*
Author to whom correspondence should be addressed.
Received: 11 July 2014 / Revised: 3 September 2014 / Accepted: 4 September 2014 / Published: 11 September 2014
(This article belongs to the Special Issue miRNA Regulation)
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Abstract

Branching epithelial morphogenesis is closely linked to epithelial-to-mesenchymal transition (EMT), a process important in normal development and cancer progression. The miR-200 family regulates epithelial morphogenesis and EMT through a negative feedback loop with the ZEB1 and ZEB2 transcription factors. miR-200 inhibits expression of ZEB1/2 mRNA, which in turn can down-regulate the miR-200 family that further results in down-regulation of E-cadherin and induction of a mesenchymal phenotype. Recent studies show that the expression of miR-200 genes is high during late pregnancy and lactation, thereby indicating that these miRs are important for breast epithelial morphogenesis and differentiation. miR-200 genes have been studied intensively in relation to breast cancer progression and metastasis, where it has been shown that miR-200 members are down-regulated in basal-like breast cancer where the EMT phenotype is prominent. There is growing evidence that the miR-200 family is up-regulated in distal breast metastasis indicating that these miRs are important for colonization of metastatic breast cancer cells through induction of mesenchymal to epithelial transition. The dual role of miR-200 in primary and metastatic breast cancer is of interest for future therapeutic interventions, making it important to understand its role and interacting partners in more detail. View Full-Text
Keywords: miRNAs; miR-200 family; breast; epithelium; branching morphogenesis; EMT; MET; breast cancer miRNAs; miR-200 family; breast; epithelium; branching morphogenesis; EMT; MET; breast cancer
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Hilmarsdottir, B.; Briem, E.; Bergthorsson, J.T.; Magnusson, M.K.; Gudjonsson, T. Functional Role of the microRNA-200 Family in Breast Morphogenesis and Neoplasia. Genes 2014, 5, 804-820.

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