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

Autor: Lihua Wang, Ergang Wang, Yi Wang, Robert Mines, Kun Xiang, Zhiguo Sun, Gaiting Zhou, Kai-Yuan Chen, Nikolai Rakhilin, Shanshan Chao, Gaoqi Ye, Zhenzhen Wu, Huiwen Yan, Hong Shen, Jeffrey Everitt, Pengcheng Bu, Xiling Shen
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: eLife, Vol 7 (2018)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.39479
Popis: 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 six 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.
Databáze: Directory of Open Access Journals