Nat Commun: Significant progress! Wang Xiaojian/Cai Xiujun of Zhejiang University has discovered a new prognostode marker for colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer death among the world.
the occurrence and development of CRC are complex and may include complex interactions between environmental exposure, diet and genetic factors.
of colorectal cancer (CRC) is associated with intestinal bacteria.
, however, the role of IRF3, the key signaling medium in innopathic sensing, has rarely been studied in CRC.
, Wang Xiaojian and Cai Xiujun of Zhejiang University co-published a research paper entitled "IRF3 prevents colorectal tumorigenesis via reseding the nuclear translocation of β-catenin" online, which found that IRF3 defective mice were highly sensitive to the development of intestinal tumors in AOM/DSS and Apcmin/plus models.
study found that cytostic IRF3 in a stationary state inhibits the occurrence of colorectal tumors by blocking the transmission of the Wnt/β-catenin signal.
IRF3 is combined with Armadillo Repeat Sequence (ARM), which is critical to the β-catenin nuclear shift and thus suppresses the β-catenin nuclear input.
, IRF3 was negatively associated with overactivation of Wnt signals in tissues of CRC, lung adenocarcinoma and hepatocellular carcinoma patients.
, the study identified IRF3 as a tumor suppressor and prognostic marker in CRC patients with unexpected mechanisms.
therefore, the study identified IRF3 as a negative regulator of the Wnt/β-catenin pathway and a potential prognostic marker for the occurrence of Wnt-related tumors, and described the link between the gut microbiome and CRC through the IRF3-β-catenin axis.
colorectal cancer (CRC) is the third leading cause of cancer death among the world.
the occurrence and development of CRC are complex and may include complex interactions between environmental exposure, diet and genetic factors.
In the pathogenesis of CRC, there are also many genetic and oscic genetic changes in proliferative signaling pathlines and anti-cancer genes, such as Wnt path, TGF-β path, (PI3K)-AKT path, MAPK pathras and tumor protein p53 (TP53).
in the case of Wnt signal transductor, β-catenin accumulates and transfers to the nucleus after Wnt is activated, binding to TCF/LEF transcription factors and promoting the proliferation of intestinal stem cells that cause tumors to occur.
symbiotic microorganisms consisting of bacteria, ancient bacteria, viruses and ethiotic organisms perch on the surface of all mucous membranes in the colon, providing a physical barrier against invading pathogens and regulating the gut environment.
interestingly, CRC tumors are often associated with dramatic changes in the microbial composition of tumors and adjacent mucous membranes, often referred to as bacterial imbalances.
emerging evidence that Kercobacteria, E. coli and fragile Bacillus play a key role in the development of colon tumors.
, the exact mechanism of intestinal bacteria in the process of CRC occurrence and development is still unclear.
intestinal bacteri groups induce congenital immune responses by triggering microbial sensors, i.e. pathogen recognition bodies (PRRs), including Tol-like subjects (TLRs), RIG-I-like subjects, NOD-like subjects (NLRs), C-type coagulation, and cytoplasmic DNA sensors.
these receptors activate the downstream protein kinases TBK1 and IKKs, followed by transcription factors IRF3 and NF-B, leading to the production of type I IFN and inflammatory factors.
It is worth noting that PRR (e.g. cGAS, TLR and NLR) and the connecting sons STING and Myd88 play a crucial role in maintaining intestinal stability and regulating the development of CRC, presumably through their secretion of TYPE I IFN, inflammatory cytokines, peptides and antimicrobials.
IRF3 is both a downstream signal transductor and transcription factor in several PRR pathways, and plays a key role in the production of type I and III interferons and various IFN stimulation genes (ISGs).
IRF3 is widely expressed in cells with different origins and is present in the cytoste in a stationary state, which is designed to be inactive.
the pathogen is detected by PRR, IRF3 is activated through TBK1 and/or IKK's phosphate at the end of the carboxyl, which mobilizes IRF3 for diogenesis and nuclear transdation, in which it acts as a transcription factor.
, DNA damage promotes anti-tumor immunity by activating cGAS-STING-IRF3 in cancer.
found that activating IRF3 through nucleic acid-induced congenital subjects is critical to intestinal stability by inducing the expression of protective Tslp and Il33 genes.
these interesting findings suggest that IRF3 is closely related to the occurrence of CRC tumors and that it is worth studying whether there are other important mechanisms.
, the study found that cytostic IRF3, which is still, inhibits the occurrence of colorectal tumors by blocking the transmission of the Wnt/β-catenin signal.
IRF3 is combined with Armadillo Repeat Sequence (ARM), which is critical to the β-catenin nuclear shift and therefore suppresses the β-catenin nuclear input.
, IRF3 was negatively associated with overactivation of Wnt signals in tissues of CRC, lung adenocarcinoma and hepatocellular carcinoma patients.
, the study identified IRF3 as a tumor suppressor and prognostic marker in CRC patients with unexpected mechanisms.