miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
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作者：
Wang L;Wang E;Wang Y;Mines R;Xiang K;Sun Z;Zhou G;Chen KY;Rakhilin N;Chao S;Ye G;Wu Z;Yan H;Shen H;Everitt J;Bu P;Shen X
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 (IL23R) 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.
