IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11452.html
   My bibliography  Save this article

miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia

Author

Listed:
  • Xi Jiang

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago)

  • Chao Hu

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago
    The First Affiliated Hospital Zhejiang University)

  • Stephen Arnovitz

    (Section of Hematology/Oncology, University of Chicago)

  • Jason Bugno

    (The University of Illinois)

  • Miao Yu

    (Howard Hughes Medical Institute, University of Chicago)

  • Zhixiang Zuo

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago
    State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Ping Chen

    (Section of Hematology/Oncology, University of Chicago)

  • Hao Huang

    (Section of Hematology/Oncology, University of Chicago)

  • Bryan Ulrich

    (Section of Hematology/Oncology, University of Chicago)

  • Sandeep Gurbuxani

    (University of Chicago)

  • Hengyou Weng

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago)

  • Jennifer Strong

    (University of Cincinnati)

  • Yungui Wang

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago
    The First Affiliated Hospital Zhejiang University)

  • Yuanyuan Li

    (Section of Hematology/Oncology, University of Chicago)

  • Justin Salat

    (Section of Hematology/Oncology, University of Chicago)

  • Shenglai Li

    (Section of Hematology/Oncology, University of Chicago)

  • Abdel G. Elkahloun

    (National Human Genome Research Institute, NIH)

  • Yang Yang

    (The University of Illinois)

  • Mary Beth Neilly

    (Section of Hematology/Oncology, University of Chicago)

  • Richard A. Larson

    (Section of Hematology/Oncology, University of Chicago)

  • Michelle M. Le Beau

    (Section of Hematology/Oncology, University of Chicago)

  • Tobias Herold

    (University Hospital Grosshadern, Ludwig-Maximilians-Universität)

  • Stefan K. Bohlander

    (University of Auckland)

  • Paul P. Liu

    (National Human Genome Research Institute, NIH)

  • Jiwang Zhang

    (Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center)

  • Zejuan Li

    (Section of Hematology/Oncology, University of Chicago
    University of Chicago)

  • Chuan He

    (Howard Hughes Medical Institute, University of Chicago)

  • Jie Jin

    (The First Affiliated Hospital Zhejiang University)

  • Seungpyo Hong

    (The University of Illinois
    Underwood International College, Yonsei University)

  • Jianjun Chen

    (University of Cincinnati
    Section of Hematology/Oncology, University of Chicago)

Abstract

MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy.

Suggested Citation

  • Xi Jiang & Chao Hu & Stephen Arnovitz & Jason Bugno & Miao Yu & Zhixiang Zuo & Ping Chen & Hao Huang & Bryan Ulrich & Sandeep Gurbuxani & Hengyou Weng & Jennifer Strong & Yungui Wang & Yuanyuan Li & J, 2016. "miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11452
    DOI: 10.1038/ncomms11452
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11452
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11452?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
    ---><---

    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:7:y:2016:i:1:d:10.1038_ncomms11452. 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.