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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Wang, E; Wang, Y; Mines, R; Xiang, K; Sun, Z; Zhou, G; Chen, K-Y; Rakhilin, N; Chao, S; Ye, G; Wu, Z; Yan, H; Shen, H; Everitt, J; Bu, P; Shen, X

Published Date

  • December 13, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 30543324

Pubmed Central ID

  • 30543324

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.39479

Language

  • eng