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

Stem Cell Research Unit, Department of Medical Faculty, Biomedical Center, University of Iceland, Vatnsmyrarvegi 16, 101 Reykjavík, Iceland
Department of Laboratory Hematology, Landspitali University Hospital, Hringbraut, 101 Reykjavík, Iceland
Department of Pharmacology and Toxicology, Medical Faculty, University of Iceland, Hofsvallagotu 53, 107 Reykjavík, Iceland
Author to whom correspondence should be addressed.
Genes 2014, 5(3), 804-820;
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)
PDF [9398 KB, uploaded 11 September 2014]


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
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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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