miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis

Lihua Wang; Ergang Wang; Yi Wang; Robert Mines; Kun Xiang; Zhiguo Sun; Gaiting Zhou; Kai-Yuan Chen; Nikolai Rakhilin; Shanshan Chao; Gaoqi Ye; Zhenzhen Wu; Huiwen Yan; Hong Shen; Jeffrey Everitt; Pengcheng Bu; Xiling Shen

doi:10.7554/eLife.39479

eLife (Dec 2018)

miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis

Lihua Wang,
Ergang Wang,
Yi Wang,
Robert Mines,
Kun Xiang,
Zhiguo Sun,
Gaiting Zhou,
Kai-Yuan Chen,
Nikolai Rakhilin,
Shanshan Chao,
Gaoqi Ye,
Zhenzhen Wu,
Huiwen Yan,
Hong Shen,
Jeffrey Everitt,
Pengcheng Bu,
Xiling Shen

Affiliations

Lihua Wang: Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Ergang Wang: ORCiD; Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Yi Wang: Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States; Affiliated Hospital of Nanjing University of TCM, Nanjing, China
Robert Mines: Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Kun Xiang: Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Zhiguo Sun: Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Gaiting Zhou: Department of Biomedical Engineering, Duke University, Durham, United States
Kai-Yuan Chen: Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Nikolai Rakhilin: Center for Genomics and Computational Biology, Duke University, Durham, United States; School of Electrical and Computer Engineering, Cornell University, New york, United States
Shanshan Chao: Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Gaoqi Ye: Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Zhenzhen Wu: Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Huiwen Yan: Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Hong Shen: Affiliated Hospital of Nanjing University of TCM, Nanjing, China
Jeffrey Everitt: Department of Pathology, Animal Pathology Core, Duke University, Durham, United States
Pengcheng Bu: ORCiD; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Xiling Shen: ORCiD; Center for Genomics and Computational Biology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United States; School of Electrical and Computer Engineering, Cornell University, New york, United States

DOI: https://doi.org/10.7554/eLife.39479
Journal volume & issue: Vol. 7

Abstract

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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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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