Llobet-Navas, DavidRodríguez-Barrueco, RuthCastro, VerónicaUgalde, Alejandro P.Sumazin, PavelJacob-Sendler, DamianDemircan, BernaCastillo Martin, MireiaPutcha, PreetiMarshall, NetoniaVillagrasa, PatriciaChan, JosephSanchez-Garcia, FélixPe'er, DanaRabadán, RaulIavarone, AntonioCordon Cardo, CarlosCalifano, AndreaLópez-Otin, CarlosEzhkova, ElenaSilva, Jose M.2020-11-272020-11-272014-04-010890-9369https://hdl.handle.net/2445/172282The 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)/503.18 p.application/pdfeng(c) Llobet-Navas, David et al., 2014EpiteliMetabolismeExpressió gènicaGlàndules mamàriesMicro RNAsGenèticaEpitheliumMetabolismGene expressionMammary glandsMicroRNAsGeneticsinfo:eu-repo/semantics/article6950042020-11-27info:eu-repo/semantics/openAccess24636986