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

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 <i>miR-34a</i> acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, <i>miR-34a</i> deficiency leads to colon tumorigenesis after <i>Citrobacter rodentium</i> infection. <i>miR-34a</i> targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. <i>miR-34a</i> 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.