IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01059-5.html
   My bibliography  Save this article

MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists

Author

Listed:
  • Cong Lv

    (College of Biological Sciences, China Agricultural University)

  • Fengyin Li

    (College of Biological Sciences, China Agricultural University)

  • Xiang Li

    (College of Biological Sciences, China Agricultural University)

  • Yuhua Tian

    (College of Biological Sciences, China Agricultural University)

  • Yue Zhang

    (Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine)

  • Xiaole Sheng

    (College of Biological Sciences, China Agricultural University)

  • Yongli Song

    (College of Biological Sciences, China Agricultural University)

  • Qingyong Meng

    (College of Biological Sciences, China Agricultural University)

  • Shukai Yuan

    (Basic Medical College, Tianjin Medical University)

  • Liming Luan

    (Vanderbilt University Medical Center)

  • Thomas Andl

    (Vanderbilt University Medical Center)

  • Xu Feng

    (State Key Laboratory of Genetic Resources and Evolution of Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Baowei Jiao

    (State Key Laboratory of Genetic Resources and Evolution of Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Mingang Xu

    (Perelman School of Medicine, University of Pennsylvania)

  • Maksim V. Plikus

    (Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine)

  • Xing Dai

    (School of Medicine, University of California)

  • Christopher Lengner

    (School of Veterinary Medicine, University of Pennsylvania
    Institute for Regenerative Medicine, University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Wei Cui

    (College of Biological Sciences, China Agricultural University
    Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London)

  • Fazheng Ren

    (College of Biological Sciences, China Agricultural University)

  • Jianwei Shuai

    (Innovation Center for Cell Signaling Network, Xiamen University)

  • Sarah E. Millar

    (Perelman School of Medicine, University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Zhengquan Yu

    (College of Biological Sciences, China Agricultural University)

Abstract

MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-κB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFβ and Wnt/β-catenin. Particularly, it activates Wnt/β-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.

Suggested Citation

  • Cong Lv & Fengyin Li & Xiang Li & Yuhua Tian & Yue Zhang & Xiaole Sheng & Yongli Song & Qingyong Meng & Shukai Yuan & Liming Luan & Thomas Andl & Xu Feng & Baowei Jiao & Mingang Xu & Maksim V. Plikus , 2017. "MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01059-5
    DOI: 10.1038/s41467-017-01059-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01059-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-017-01059-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xing Yang & Haibo Xu & Xu Yang & Hui Wang & Li Zou & Qin Yang & Xiaopeng Qi & Li Li & Hongxia Duan & Xiyun Yan & Nai Yang Fu & Jing Tan & Zongliu Hou & Baowei Jiao, 2024. "Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01059-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.