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

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.