miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
- Duke University, United States
- Chinese Academy of Sciences, China
- Affiliated Hospital of Nanjing University of TCM, China
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
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.
Ethics
Animal experimentation: Mouse maintenance and procedures were approved by Duke University DLAR and followed the protocol (A286-15-10).
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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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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