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Elife. 2017 Sep 5;6. pii: e29538. doi: 10.7554/eLife.29538.

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

Author information

1
Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
2
Vanderbilt University Medical Center, Nashville, United States.
3
Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, Center for Complex Biological Systems, University of California, Irvine, Irvine, United States.
4
Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, China.
5
Department of Physics and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Xiamen University, Xiamen, China.
6
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States.
7
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, United States.
8
Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom.

Abstract

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.

KEYWORDS:

BMP; Wnt; colorectal cancer; developmental biology; intestinal stem cell; miR-31; mouse; regeneration; stem cells

PMID:
28870287
PMCID:
PMC5584991
DOI:
10.7554/eLife.29538
[Indexed for MEDLINE]
Free PMC Article

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