miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6.

Autor: Nekritz EA; Graduate School, Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA., Rodriguez-Barrueco R; Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Anatomy Unit, Department of Pathology and Experimental Therapy, School of Medicine, University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain., Yan KK; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Davis ML; Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Werner RL; Graduate School, Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA., Devis-Jauregui L; Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Mukhopadhyay P; Graduate School, Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA., Yu J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Llobet-Navas D; Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain., Silva J; Graduate School, Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2021 Dec 06; Vol. 22 (12), pp. e53201. Date of Electronic Publication: 2021 Oct 11.
DOI: 10.15252/embr.202153201
Abstrakt: During the female lifetime, the expansion of the epithelium dictated by the ovarian cycles is supported by a transient increase in the mammary epithelial stem cell population (MaSCs). Notably, activation of Wnt/β-catenin signaling is an important trigger for MaSC expansion. Here, we report that the miR-424/503 cluster is a modulator of canonical Wnt signaling in the mammary epithelium. We show that mammary tumors of miR-424(322)/503-depleted mice exhibit activated Wnt/β-catenin signaling. Importantly, we show a strong association between miR-424/503 deletion and breast cancers with high levels of Wnt/β-catenin signaling. Moreover, miR-424/503 cluster is required for Wnt-mediated MaSC expansion induced by the ovarian cycles. Lastly, we show that miR-424/503 exerts its function by targeting two binding sites at the 3'UTR of the LRP6 co-receptor and reducing its expression. These results unveil an unknown link between the miR-424/503, regulation of Wnt signaling, MaSC fate, and tumorigenesis.
(© 2021 The Authors.)
Databáze: MEDLINE
Externí odkaz: