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Nekritz EA, Rodriguez-Barrueco R, Yan KK, et al. miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6. EMBO Rep. 2021;22(12):e53201doi: 10.15252/embr.202153201.
Nekritz, E. A., Rodriguez-Barrueco, R., Yan, K. K., Davis, M. L., Werner, R. L., Devis-Jauregui, L., Mukhopadhyay, P., Yu, J., Llobet-Navas, D., & Silva, J. (2021). miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6. EMBO reports, 22(12), e53201. https://doi.org/10.15252/embr.202153201
Nekritz, Erin A, et al. "miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6." EMBO reports vol. 22,12 (2021): e53201. doi: https://doi.org/10.15252/embr.202153201
Nekritz EA, Rodriguez-Barrueco R, Yan KK, Davis ML, Werner RL, Devis-Jauregui L, Mukhopadhyay P, Yu J, Llobet-Navas D, Silva J. miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6. EMBO Rep. 2021 Dec 06;22(12):e53201. doi: 10.15252/embr.202153201. Epub 2021 Oct 11. PMID: 34633138; PMCID: PMC8647148.
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EMBO Rep. 2021 Dec 06;22(12):e53201. doi: 10.15252/embr.202153201. Epub 2021 Oct 11.

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

EMBO reports

Erin A Nekritz, Ruth Rodriguez-Barrueco, Koon-Kiu Yan, Meredith L Davis, Rachel L Werner, Laura Devis-Jauregui, Partha Mukhopadhyay, Jiyang Yu, David Llobet-Navas, Jose Silva

Affiliations

  1. Graduate School, Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
  2. Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  3. Anatomy Unit, Department of Pathology and Experimental Therapy, School of Medicine, University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain.
  4. Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  5. Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
  6. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

PMID: 34633138 PMCID: PMC8647148 DOI: 10.15252/embr.202153201

Abstract

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.

Keywords: LRP6; Wnt/β-catenin; breast cancer; miR-424/503

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