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The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland
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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.
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LLOBET-NAVAS, David, et al. The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland. Genes & Development. 2014. Vol. 28, num. 7, pags. 765-782. ISSN 0890-9369. [consulted: 30 of May of 2026]. Available at: https://hdl.handle.net/2445/172282