IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8151.html
   My bibliography  Save this article

The oncogenic microRNA miR-21 promotes regulated necrosis in mice

Author

Listed:
  • Xiaodong Ma

    (Lerner Research Institute, Cleveland Clinic
    Institute of Pharmaceutical Research, South China Normal University)

  • Daniel J. Conklin

    (Diabetes and Obesity Center, University of Louisville)

  • Fenge Li

    (Diabetes and Obesity Center, University of Louisville)

  • Zhongping Dai

    (Fox Chase Cancer Center, Institute for Cancer Research)

  • Xiang Hua

    (Fox Chase Cancer Center, Institute for Cancer Research)

  • Yan Li

    (School of Medicine, University of Louisville)

  • Zijun Y. Xu-Monette

    (MD Anderson Cancer Center)

  • Ken H. Young

    (MD Anderson Cancer Center)

  • Wei Xiong

    (Cancer Research Institute, Central South University)

  • Marcin Wysoczynski

    (Diabetes and Obesity Center, University of Louisville)

  • Srinivas D. Sithu

    (Diabetes and Obesity Center, University of Louisville)

  • Sanjay Srivastava

    (Diabetes and Obesity Center, University of Louisville)

  • Aruni Bhatnagar

    (Diabetes and Obesity Center, University of Louisville)

  • Yong Li

    (Lerner Research Institute, Cleveland Clinic)

Abstract

MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumour necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis and miR-21 enhances cellular necrosis by negatively regulating tumour suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway, and could be a therapeutic target for preventing pathologic necrosis.

Suggested Citation

  • Xiaodong Ma & Daniel J. Conklin & Fenge Li & Zhongping Dai & Xiang Hua & Yan Li & Zijun Y. Xu-Monette & Ken H. Young & Wei Xiong & Marcin Wysoczynski & Srinivas D. Sithu & Sanjay Srivastava & Aruni Bh, 2015. "The oncogenic microRNA miR-21 promotes regulated necrosis in mice," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8151
    DOI: 10.1038/ncomms8151
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8151
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8151?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. Ruiling Liu & Cuilian Liu & Xiaozhen He & Peng Sun & Bin Zhang & Haoran Yang & Weiyun Shi & Qingguo Ruan, 2022. "MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake," Nature Communications, Nature, vol. 13(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:6:y:2015:i:1:d:10.1038_ncomms8151. 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.