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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miR-34a 是柠檬酸杆菌诱导的炎症性结肠肿瘤发生的 microRNA 保障
DOI：
10.7554/elife.39479
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发表时间：
2018-12-13
期刊：
影响因子：
7.7
通讯作者：
Shen, Xiling
中科院分区：
文献类型：
--
作者：
Wang, Lihua;Wang, Ergang;Shen, Xiling
炎症常常诱导再生来修复组织损伤。然而，慢性炎症可将暂时性增生转化为肿瘤发生的肥沃土壤。在这里，我们证明了microRNA miR-34a是保护炎症干细胞生态位和修复性再生的核心保障。尽管miR-34a缺乏在正常体内平衡中作用不大，但它会导致鼠柠檬酸杆菌感染后结肠肿瘤的发生。miR-34a同时靶向免疫细胞和上皮细胞，抑制炎症诱导的干细胞增殖。miR-34a靶向白细胞介素6受体（IL-6R）和白细胞介素23受体（IL-23R）抑制辅助性T细胞17 （Th17）的分化和扩增，靶向趋化因子CCL22阻碍Th17细胞向结肠上皮募集，靶向孤儿受体白细胞介素17受体D （IL-17RD）抑制il -17诱导的干细胞增殖。我们的研究强调了microRNAs在炎症期间保护干细胞生态位的重要性，尽管它们在正常组织稳态中缺乏功能。
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.