TY - JOUR TI - Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis AU - Tian, Yuhua AU - Ma, Xianghui AU - Lv, Cong AU - Sheng, Xiaole AU - Li, Xiang AU - Zhao, Ran AU - Song, Yongli AU - Andl, Thomas AU - Plikus, Maksim V AU - Sun, Jinyue AU - Ren, Fazheng AU - Shuai, Jianwei AU - Lengner, Christopher J AU - Cui, Wei AU - Yu, Zhengquan A2 - Nusse, Roel VL - 6 PY - 2017 DA - 2017/09/05 SP - e29538 C1 - eLife 2017;6:e29538 DO - 10.7554/eLife.29538 UR - https://doi.org/10.7554/eLife.29538 AB - 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, TGFβ 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. KW - miR-31 KW - intestinal stem cell KW - colorectal cancer KW - regeneration KW - Wnt KW - BMP JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -