title: RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Rig-I could regulate gut microbiota through regulating IgA and IL6-STAT3-dependent Reg3γ expression. Besides, Rig-I could inhibit CRC progression.
authors.affiliation: 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.|Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China. jue_hp@yeah.net.|Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. jue_hp@yeah.net.
authors.forename: Houbao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China.
authors.forename: Wang-Yang
authors.initials: WY
authors.lastname: Xu
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Center for Bioinformation Technology, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China.
authors.forename: Shunyuan
authors.initials: S
authors.lastname: Lu
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. ccwei@sjtu.edu.cn.|Shanghai Center for Bioinformation Technology, Shanghai, China. ccwei@sjtu.edu.cn.|Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. ccwei@sjtu.edu.cn.
authors.forename: Chaochun
authors.initials: C
authors.lastname: Wei
authors.affiliation: 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.|Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China. zhugangw@shsmu.edu.cn.|Shanghai Research Center for Model Organisms, Shanghai, China. zhugangw@shsmu.edu.cn.|Research Center for Experimental Medicine, Rui-Jin Hospital, 197 Ruijin Road II, Shanghai, 200025, China. zhugangw@shsmu.edu.cn.
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects; D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000382:microbiology*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D000073718:Pancreatitis-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000097905:Roundabout Proteins
chemical_list: D001397:Azoxymethane; D004269:DNA, Bacterial; D016264:Dextran Sulfate; D007070:Immunoglobulin A; D015850:Interleukin-6; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D050796:STAT3 Transcription Factor; C437968:PLAAT4 protein, human; C494437:REG3G protein, human; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins
keywords: Colorectal cancer; Gut microbiota; High-throughput sequencing; Mouse model; Rig-I