TY - JOUR
T1 - The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland
AU - Llobet-Navas, David
AU - Rodríguez-Barrueco, Ruth
AU - Castro, Verónica
AU - Ugalde, Alejandro P.
AU - Sumazin, Pavel
AU - Jacob-Sendler, Damian
AU - Demircan, Berna
AU - Castillo-Martín, Mireia
AU - Putcha, Preeti
AU - Marshall, Netonia
AU - Villagrasa, Patricia
AU - Chan, Joseph
AU - Sanchez-Garcia, Félix
AU - Pe'er, Dana
AU - Rabadán, Raul
AU - Iavarone, Antonio
AU - Cordón-Cardó, Carlos
AU - Califano, Andrea
AU - López-Otín, Carlos
AU - Ezhkova, Elena
AU - Silva, Jose M.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
KW - BCL2
KW - IGF1R
KW - Mammary gland development
KW - TGFβ
KW - miR-424
KW - miR-503
UR - http://www.scopus.com/inward/record.url?scp=84898869604&partnerID=8YFLogxK
U2 - 10.1101/gad.237404.114
DO - 10.1101/gad.237404.114
M3 - Article
C2 - 24636986
AN - SCOPUS:84898869604
SN - 0890-9369
VL - 28
SP - 765
EP - 782
JO - Genes and Development
JF - Genes and Development
IS - 7
ER -