1. Cancer Biology

miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis

  1. Lihua Wang
  2. Ergang Wang
  3. Yi Wang
  4. Robert Mines
  5. Kun Xiang
  6. Zhiguo Sun
  7. Gaiting Zhou
  8. Kai-Yuan Chen
  9. Nikolai Rakhilin
  10. Shanshan Chao
  11. Gaoqi Ye
  12. Zhenzhen Wu
  13. Huiwen Yan
  14. Hong Shen
  15. Jeffrey Everitt
  16. Pengcheng Bu  Is a corresponding author
  17. Xiling Shen  Is a corresponding author
  1. Duke University, United States
  2. Chinese Academy of Sciences, China
  3. Affiliated Hospital of Nanjing University of TCM, China
https://doi.org/10.7554/eLife.39479
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Cite this article
  1. Lihua Wang
  2. Ergang Wang
  3. Yi Wang
  4. Robert Mines
  5. Kun Xiang
  6. Zhiguo Sun
  7. Gaiting Zhou
  8. Kai-Yuan Chen
  9. Nikolai Rakhilin
  10. Shanshan Chao
  11. Gaoqi Ye
  12. Zhenzhen Wu
  13. Huiwen Yan
  14. Hong Shen
  15. Jeffrey Everitt
  16. Pengcheng Bu
  17. Xiling Shen
(2018)
miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
eLife 7:e39479.
https://doi.org/10.7554/eLife.39479
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Abstract

Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin 6 receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17 induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.

Data availability

The RNA-seq data have been included as Figure 8-source data 1 and 2.

Article and author information

Author details

  1. Lihua Wang

    Department of Biomedical Engineering, Duke University, Durhuam, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Ergang Wang

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Yi Wang

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Robert Mines

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Kun Xiang

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Zhiguo Sun

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Gaiting Zhou

    Department of Biomedical Engineering, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Kai-Yuan Chen

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Nikolai Rakhilin

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Shanshan Chao

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Gaoqi Ye

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Zhenzhen Wu

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  13. Huiwen Yan

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  14. Hong Shen

    Affiliated Hospital of Nanjing University of TCM, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  15. Jeffrey Everitt

    Department of Pathology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  16. Pengcheng Bu

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    For correspondence
    bupc@ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3208-0354

  17. Xiling Shen

    Center for Genomics and Computational Biology, Duke University, Durham, United States
    For correspondence
    xs37@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4978-3531

Funding

National Institute of General Medical Sciences (R35GM122465)

  • Xiling Shen

National Cancer Institute (U01CA214300)

  • Xiling Shen

National Science Foundation (1350659)

  • Xiling Shen

National Cancer Institute (U01CA217514)

  • Xiling Shen

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

Reviewing Editor

  1. Elaine Fuchs, Howard Hughes Medical Institute, The Rockefeller University, United States

Ethics

Animal experimentation: Mouse maintenance and procedures were approved by Duke University DLAR and followed the protocol (A286-15-10).

Version history

  1. Received: June 22, 2018
  2. Accepted: December 6, 2018
  3. Accepted Manuscript published: December 13, 2018 (version 1)
  4. Version of Record published: January 2, 2019 (version 2)

Copyright

© 2018, Wang 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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  1. Lihua Wang
  2. Ergang Wang
  3. Yi Wang
  4. Robert Mines
  5. Kun Xiang
  6. Zhiguo Sun
  7. Gaiting Zhou
  8. Kai-Yuan Chen
  9. Nikolai Rakhilin
  10. Shanshan Chao
  11. Gaoqi Ye
  12. Zhenzhen Wu
  13. Huiwen Yan
  14. Hong Shen
  15. Jeffrey Everitt
  16. Pengcheng Bu
  17. Xiling Shen
(2018)
miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
eLife 7:e39479.
https://doi.org/10.7554/eLife.39479

Share this article

https://doi.org/10.7554/eLife.39479

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