miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
| Autor: | Kai-Yuan Chen, Ergang Wang, Gaiting Zhou, Yi Wang, Zhenzhen Wu, Hong Shen, Huiwen Yan, Nikolai Rakhilin, Jeffrey I. Everitt, Lihua Wang, Xiling Shen, Zhiguo Sun, Kun Xiang, Robert Mines, Gaoqi Ye, Shanshan Chao, Pengcheng Bu |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mouse QH301-705.5 Cellular differentiation Science Inflammation Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences microRNA medicine Biology (General) Tissue homeostasis Cancer Biology Orphan receptor General Immunology and Microbiology General Neuroscience Interleukin General Medicine stem cell 030104 developmental biology colon cancer inflammation Cancer research Medicine Citrobacter rodentium Th17 Stem cell medicine.symptom Carcinogenesis Research Article |
| Zdroj: | eLife eLife, Vol 7 (2018) |
| ISSN: | 2050-084X |
| 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: | OpenAIRE |
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