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|Title:||The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland|
Ugalde, Alejandro P.
Castillo Martin, Mireia
Cordon Cardo, Carlos
Silva, Jose M.
|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: https://doi.org/10.1101/gad.237404.114|
|It is part of:||Genes & Development, 2014, vol. 28, num. 7, p. 765-782|
|Appears in Collections:||Articles publicats en revistes (Patologia i Terapèutica Experimental)|
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