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. © 2017 the author(s).