1. Immunology and Inflammation
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MicroRNA-122 supports robust innate immunity in hepatocytes by targeting the RTKs/STAT3 signaling pathway

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Cite this article as: eLife 2019;8:e41159 doi: 10.7554/eLife.41159

Abstract

MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and a central player in liver biology and disease. Herein, we report a previously unknown role for miR-122 in hepatocyte intrinsic innate immunity. Restoring miR-122 levels in hepatoma cells markedly enhanced the activation of interferons (IFNs) in response to a variety of viral nucleic acids or simulations, especially of hepatitis C virus RNA and poly (I:C). Mechanistically, miR-122 down-regulated the phosphorylation (Tyr705) of STAT3 and thereby removed the negative regulation of STAT3 on IFN-signaling. While STAT3 represses IFN expression by inhibiting interferon regulatory factor 1 (IRF1), miR-122 targets MERTK, FGFR1 and IGF1R, three receptor tyrosine kinases (RTKs) that directly promote STAT3 phosphorylation. This work identifies a miR-122-RTKs/STAT3-IRF1-IFNs regulatory circuitry, which may play a pivotal role in regulating hepatocyte innate immunity. These findings renewed our knowledge about miR-122's function and have important implications for treating hepatitis viruses.

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Author details

  1. Hui Xu

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Shi-Jun Xu

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Shu-Juan Xie

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yin Zhang

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Jian-Hua Yang

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3863-2786
  6. Wei-Qi Zhang

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Man-Ni Zheng

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Hui Zhou

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Liang-Hu Qu

    School of Life Sciences, Sun Yat-sen University, Guangzhou, China
    For correspondence
    lssqlh@mail.sysu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3657-2863

Funding

National Natural Science Foundation of China (31200593)

  • Hui Xu

National Natural Science Foundation of China (31230042)

  • Liang-Hu Qu

National Natural Science Foundation of China (31471223)

  • Liang-Hu Qu

National Natural Science Foundation of China (31671349)

  • Liang-Hu Qu

Natural Science Foundation of Guangdong Province (2014A030313163)

  • Hui Xu

National Basic Research Program of China (2011CB811300)

  • Liang-Hu Qu

National Key R&D Program of China (2017YFA0504400)

  • Jian-Hua Yang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: August 16, 2018
  2. Accepted: February 7, 2019
  3. Accepted Manuscript published: February 8, 2019 (version 1)
  4. Version of Record published: February 25, 2019 (version 2)

Copyright

© 2019, Xu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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