Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis

文献类型： 外文期刊

第一作者： Tian, Yuhua

作者： Tian, Yuhua;Ma, Xianghui;Lv, Cong;Sheng, Xiaole;Li, Xiang;Zhao, Ran;Song, Yongli;Ren, Fazheng;Yu, Zhengquan;Tian, Yuhua;Ma, Xianghui;Lv, Cong;Sheng, Xiaole;Li, Xiang;Zhao, Ran;Song, Yongli;Ren, Fazheng;Yu, Zhengquan;Andl, Thomas;Plikus, Maksim, V;Sun, Jinyue;Shuai, Jianwei;Shuai, Jianwei;Lengner, Christopher J.;Lengner, Christopher J.;Cui, Wei

作者机构：

期刊名称：ELIFE （ 影响因子：8.14； 五年影响因子：9.056 ）

ISSN： 2050-084X

年卷期： 2017 年 6 卷

页码：

收录情况： SCI

摘要： Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGF beta signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

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