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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer

Authors: Houbao Zhu, Wang-Yang Xu, Zhiqiang Hu, Hongxin Zhang, Yan Shen, Shunyuan Lu, Chaochun Wei, Zhu-Gang Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

Retinoic acid-inducible gene-I (Rig-I) is an intracellular viral RNA receptor, which specifically recognizes double-stranded viral RNA initiating antiviral innate immunity. Increasing evidences showed that Rig-I had broader roles in antibacterial immunity and cancer protection. However, the potential roles and mechanisms of Rig-I in gut flora regulation and colorectal cancer (CRC) progression remain unclear.

Methods

Immunohistochemistry was performed to detect Rig-I protein in 38 pairs of CRC tissue and matched adjacent mucosa, and immunofluorescence and western blot were also used to detect Rig-I protein expression in AOM/DSS-induced mice CRC samples. High-throughput sequencing was conducted to evaluate gut microbiota changes in Rig-I-deficient mice. Immunofluorescence and flow cytometry were used to detect IgA expression. Additionally, real-time quantitative PCR was performed to detect RNA expression in mouse intestines and cultured cells, and western blot was used to detect phosphorylation of STAT3 in IL-6-stimulated B cell line.

Results

Rig-I was downregulated in human and mouse CRC samples and Rig-I-deficient mice were more susceptible to AOM/DSS-induced colitis-associated colorectal cancer (CAC). Furthermore, Rig-I-deficient mice displayed gut microbiota disturbance compared to wild type mice. IgA, Reg3γ and Pdcd1 levels were decreased in intestines of Rig-I-deficient mice. Phosphorylation of STAT3 in IL-6-stimulated 1B4B6 was decreased.

Conclusion

Rig-I could regulate gut microbiota through regulating IgA and IL6-STAT3-dependent Reg3γ expression. Besides, Rig-I could inhibit CRC progression.
Appendix
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Metadata
Title
RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer
Authors
Houbao Zhu
Wang-Yang Xu
Zhiqiang Hu
Hongxin Zhang
Yan Shen
Shunyuan Lu
Chaochun Wei
Zhu-Gang Wang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0471-3

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