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.
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RNA 病毒受体 Rig-I 监测肠道微生物群并抑制结肠炎相关结直肠癌
DOI：
10.1186/s13046-016-0471-3
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发表时间：
2017-01-05
期刊：
影响因子：
--
通讯作者：
Wang ZG
中科院分区：
文献类型：
--
作者：
Zhu H;Xu WY;Hu Z;Zhang H;Shen Y;Lu S;Wei C;Wang ZG
背景视黄酸诱导基因-I（Retinoicacid-induciblegene-I，Rig-I）是一种细胞内病毒RNA受体，特异性识别双链病毒RNA，启动抗病毒天然免疫。越来越多的证据表明Rig-I在抗菌免疫和肿瘤保护中具有广泛的作用。方法采用免疫组化法检测38对大肠植物群组织及癌旁组织中Rig-I蛋白的表达，免疫荧光法和western blot法检测AOM/DSS诱导的小鼠大肠癌组织中Rig-I蛋白的表达。进行高通量测序以评估Rig-I缺陷小鼠肠道微生物群的变化。免疫荧光和流式细胞术检测伊加表达。结果Rig-I在人和小鼠结直肠癌组织中表达下调，Rig-I缺陷小鼠对AOM/DSS诱导的结肠炎相关性结直肠癌（CAC）的易感性增加。此外，与野生型小鼠相比，Rig-I缺陷小鼠显示肠道微生物群紊乱。Rig-I缺陷小鼠肠道伊加、Reg 3 γ和Pdcd 1水平降低。结论Rig-I可通过调节伊加和IL-6-STAT 3依赖的Reg 3 γ的表达来调节肠道菌群。此外，Rig-I可以抑制CRC进展。
BackgroundRetinoic 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.MethodsImmunohistochemistry 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 inRig-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.ResultsRig-I was downregulated in human and mouse CRC samples andRig-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 ofRig-I-deficient mice. Phosphorylation of STAT3 in IL-6-stimulated 1B4B6 was decreased.ConclusionRig-I could regulate gut microbiota through regulating IgA and IL6-STAT3-dependent Reg3γ expression. Besides, Rig-I could inhibit CRC progression.