GSE155777 IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin

Contributors : Miao Tian ; Xiaojian WangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOccurrence of Colorectal cancer （CRC）is relevant with gut microbiota. However, role of IRF3, a key signaling mediator in innate immune sensing, has been barely investigated in CRC. Here, we unexpectedly found that the IRF3 deficient mice are hyper-susceptible to the development of intestinal tumor in AOM/DSS and Apcmin/+ model s. Genetic ablation of IRF3 profoundly promotes the proliferation of intestinal epithelial cells via aberrantly activating Wnt signaling. Mechanically, IRF3 in resting state robustly associates with the active β-catenin in the cytoplasm, thus preventing its nuclear translocation and cell proliferat ion, which can be relieved upon microbe-induced activation of IRF3. In accordance, the survival of CRC is clinically correlated with the expression level of IRF3. Therefore, our study identifies IRF3 as a negative regulator of the Wnt/β-catenin pathway and a potential prognosis marker for Wnt-relat ed tumorigenesis, and describes an intriguing link between gut microbiota and CRC via the IRF3-β-catenin axis.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research