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Title: The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland
Author: Llobet-Navas, David
Rodríguez-Barrueco, Ruth
Castro, Verónica
Ugalde, Alejandro P.
Sumazin, Pavel
Jacob-Sendler, Damian
Demircan, Berna
Castillo Martin, Mireia
Putcha, Preeti
Marshall, Netonia
Villagrasa, Patricia
Chan, Joseph
Sanchez-Garcia, Félix
Pe'er, Dana
Rabadán, Raul
Iavarone, Antonio
Cordon Cardo, Carlos
Califano, Andrea
López-Otin, Carlos
Ezhkova, Elena
Silva, Jose M.
Keywords: Epiteli
Expressió gènica
Glàndules mamàries
Micro RNAs
Gene expression
Mammary glands
Issue Date: 1-Apr-2014
Publisher: Cold Spring Harbor Laboratory Press
Abstract: The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy. Through the generation of a knockout mouse model, we found that regression of the secretory acini of the mammary gland was compromised in the absence of miR-424(322)/503. Mechanistically, we show that miR-424(322)/503 orchestrates cell life and death decisions by targeting BCL-2 and IGF1R (insulin growth factor-1 receptor). Furthermore, we demonstrate that the expression of this microRNA cluster is regulated by TGF-β, a well-characterized regulator of mammary involution. Overall, our data suggest a model in which activation of the TGF-β pathway after weaning induces the transcription of miR-424(322)/503, which in turn down-regulates the expression of key genes. Here, we unveil a previously unknown, multilayered regulation of epithelial tissue remodeling coordinated by the microRNA cluster miR-424(322)/503.
Note: Reproducció del document publicat a:
It is part of: Genes & Development, 2014, vol. 28, num. 7, p. 765-782
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ISSN: 0890-9369
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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