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

Publication ,  Journal Article
Wang, L; Wang, E; Wang, Y; Mines, R; Xiang, K; Sun, Z; Zhou, G; Chen, K-Y; Rakhilin, N; Chao, S; Ye, G; Wu, Z; Yan, H; Shen, H; Everitt, J ...
Published in: Elife
December 13, 2018

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.

Duke Scholars

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 13, 2018

Volume

7

Location

England

Related Subject Headings

  • Th17 Cells
  • Receptors, Interleukin
  • Neoplastic Stem Cells
  • MicroRNAs
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Male
  • Inflammation
  • Gene Expression Profiling
 

Citation

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Wang, L., Wang, E., Wang, Y., Mines, R., Xiang, K., Sun, Z., … Shen, X. (2018). miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis. Elife, 7. https://doi.org/10.7554/eLife.39479
Wang, Lihua, Ergang Wang, Yi Wang, Robert Mines, Kun Xiang, Zhiguo Sun, Gaiting Zhou, et al. “miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.Elife 7 (December 13, 2018). https://doi.org/10.7554/eLife.39479.
Wang L, Wang E, Wang Y, Mines R, Xiang K, Sun Z, et al. miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis. Elife. 2018 Dec 13;7.
Wang, Lihua, et al. “miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.Elife, vol. 7, Dec. 2018. Pubmed, doi:10.7554/eLife.39479.
Wang L, Wang E, Wang Y, Mines R, Xiang K, Sun Z, Zhou G, Chen K-Y, Rakhilin N, Chao S, Ye G, Wu Z, Yan H, Shen H, Everitt J, Bu P, Shen X. miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis. Elife. 2018 Dec 13;7.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 13, 2018

Volume

7

Location

England

Related Subject Headings

  • Th17 Cells
  • Receptors, Interleukin
  • Neoplastic Stem Cells
  • MicroRNAs
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Male
  • Inflammation
  • Gene Expression Profiling