2. Academic Validation
  3. RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer

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

  • J Exp Clin Cancer Res. 2017 Jan 5;36(1):2. doi: 10.1186/s13046-016-0471-3.
Houbao Zhu 1 2 3,  Wang-Yang Xu 4 5,  Zhiqiang Hu 6 7,  Hongxin Zhang 4 5,  Yan Shen 4,  Shunyuan Lu 4 5,  Chaochun Wei 8 9 10,  Zhu-Gang Wang 11 12 13 14
Affiliations

Affiliations

  • 1 State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jue_hp@yeah.net.
  • 2 Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China. jue_hp@yeah.net.
  • 3 Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. jue_hp@yeah.net.
  • 4 State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China.
  • 6 School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • 7 Shanghai Center for Bioinformation Technology, Shanghai, China.
  • 8 School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. ccwei@sjtu.edu.cn.
  • 9 Shanghai Center for Bioinformation Technology, Shanghai, China. ccwei@sjtu.edu.cn.
  • 10 Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. ccwei@sjtu.edu.cn.
  • 11 State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhugangw@shsmu.edu.cn.
  • 12 Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China. zhugangw@shsmu.edu.cn.
  • 13 Shanghai Research Center for Model Organisms, Shanghai, China. zhugangw@shsmu.edu.cn.
  • 14 Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. zhugangw@shsmu.edu.cn.
PMID: 28057020 DOI: 10.1186/s13046-016-0471-3
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.

Keywords

Colorectal cancer; Gut microbiota; High-throughput sequencing; Mouse model; Rig-I.

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