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2014-04-01

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The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland

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https://doi.org/10.1101/gad.237404.114

Resum

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.

Matèries

Epiteli, Metabolisme, Expressió gènica, Glàndules mamàries, Micro RNAs, Genètica

Matèries (anglès)

Epithelium, Metabolism, Gene expression, Mammary glands, MicroRNAs, Genetics

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Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

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.. The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland. _Genes & Development_. 2014. Vol. 28, núm. 7, pàgs. 765-782. [consulta: 9 de gener de 2026]. ISSN: 0890-9369. [Disponible a: https://hdl.handle.net/2445/172282]

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