IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6202.html
   My bibliography  Save this article

Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression

Author

Listed:
  • Rajesha Rupaimoole

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center)

  • Sherry Y. Wu

    (The University of Texas MD Anderson Cancer Center)

  • Sunila Pradeep

    (The University of Texas MD Anderson Cancer Center)

  • Cristina Ivan

    (The University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center)

  • Chad V. Pecot

    (University of North Carolina Lineberger Comprehensive Cancer Center)

  • Kshipra M. Gharpure

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center)

  • Archana S. Nagaraja

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center)

  • Guillermo N. Armaiz-Pena

    (The University of Texas MD Anderson Cancer Center)

  • Michael McGuire

    (The University of Texas MD Anderson Cancer Center)

  • Behrouz Zand

    (The University of Texas MD Anderson Cancer Center)

  • Heather J. Dalton

    (The University of Texas MD Anderson Cancer Center)

  • Justyna Filant

    (The University of Texas MD Anderson Cancer Center)

  • Justin Bottsford Miller

    (The University of Texas MD Anderson Cancer Center)

  • Chunhua Lu

    (The University of Texas MD Anderson Cancer Center)

  • Nouara C. Sadaoui

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center)

  • Lingegowda S. Mangala

    (The University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center)

  • Morgan Taylor

    (The University of Texas MD Anderson Cancer Center)

  • Twan van den Beucken

    (University of Toronto, Toronto)

  • Elizabeth Koch

    (University of Toronto, Toronto
    Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network)

  • Cristian Rodriguez-Aguayo

    (Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Li Huang

    (The University of Texas MD Anderson Cancer Center)

  • Menashe Bar-Eli

    (The University of Texas MD Anderson Cancer Center)

  • Bradly G. Wouters

    (University of Toronto, Toronto
    Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network)

  • Milan Radovich

    (Microbiology and Immunology, Indiana University)

  • Mircea Ivan

    (Microbiology and Immunology, Indiana University)

  • George A. Calin

    (Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Wei Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Gabriel Lopez-Berestein

    (Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Anil K. Sood

    (The University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Cancer-related deregulation of miRNA biogenesis has been suggested, but the underlying mechanisms remain elusive. Here we report a previously unrecognized effect of hypoxia in the downregulation of Drosha and Dicer in cancer cells that leads to dysregulation of miRNA biogenesis and increased tumour progression. We show that hypoxia-mediated downregulation of Drosha is dependent on ETS1/ELK1 transcription factors. Moreover, mature miRNA array and deep sequencing studies reveal altered miRNA maturation in cells under hypoxic conditions. At a functional level, this phenomenon results in increased cancer progression in vitro and in vivo, and data from patient samples are suggestive of miRNA biogenesis downregulation in hypoxic tumours. Rescue of Drosha by siRNAs targeting ETS1/ELK1 in vivo results in significant tumour regression. These findings provide a new link in the mechanistic understanding of global miRNA downregulation in the tumour microenvironment.

Suggested Citation

  • Rajesha Rupaimoole & Sherry Y. Wu & Sunila Pradeep & Cristina Ivan & Chad V. Pecot & Kshipra M. Gharpure & Archana S. Nagaraja & Guillermo N. Armaiz-Pena & Michael McGuire & Behrouz Zand & Heather J. , 2014. "Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6202
    DOI: 10.1038/ncomms6202
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6202
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6202?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:5:y:2014:i:1:d:10.1038_ncomms6202. 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.