TIPE Regulates DcR3 Expression And Promotes Colorectal Cancer Proliferation And Migration By Activating The PI3K/AKT Signaling Pathway

Background:Colorectal cancer(CRC)is currently the fourth most deadly cancer all over the world,and it seriously endangers human health.Although surgery,chemotherapy,radiotherapy and molecular targeted therapy have a certain role in the current treatment of CRC,the cure rate and survival rate of patients are still low.Therefore,basic research on CRC is imminent.Tumor necrosis factor induced protein-8(TIPE)is highly expressed in CRC.Our previous research confirms that TIPE can regulate VEGFR2 expression and promote angiogenesis and metastasis of CRC.Decoy Receptor 3(DcR3)is a soluble secreted protein,which can antagonize FasL-induced apoptosis and promote tumorigenesis.Our previous studies found that DcR3 is highly expressed in gastric cancer and positively correlated with TIPE.The relationship between TIPE and DcR3 is unclear.Thus,we will explore whether TIPE can regulate the expression of DcR3 and the specific molecular mechanism.Methods:Using bioinformatics and tissue microarray to determine the expression and correlation of TIPE and DcR3 in CRC.The expression of TIPE and DcR3 in colon cancer cells were detected.DcR3 secretion from CRC patients was collected and detected by ELISA.Then the double luciferase reporter gene analyzed the interaction between TIPE and DcR3.Exogenous change TIPE expression and analyze its function and influence on DcR3 secretion.Using LPS to stimulate TIPE overexpressed HCT116 cells,detecting DcR3 secretion and signaling pathway,then using inhibitors to confirm the molecular mechanisms involved.Results:We found that TIPE and DcR3 were highly expressed in CRC patients and their expression was positively correlated,the expression of TIPE and DcR3 was related to poor prognosis in CRC patients.DcR3 was highly expressed in plasma of cancer patients.In vitro cell experiments confirmed that TIPE and DcR3 were highly expressed in HCT116 cell line.The double luciferase reporter gene analysis showed that TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter.LPS-stimulated TIPE overexpressing HCT116 cells confirmed that the PI3K/AKT signaling pathway was activated,which in turn regulated DcR3 expression to promote cell proliferation,migration and inhibit apoptosis.Tissue microarray analysis further indicated that the expression of TIPE and DcR3 were increased in CRC,and the expression of TIPE was positively correlated with CRC metastasis and poor prognosis in patients.Conclusions:TIPE and DcR3 are highly expressed in CRC and both are associated with poor prognosis.Besides,TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC,thus promoting cell proliferation,migration and inhibiting apoptosis.These may have good clinical significance and application prospect for the treatment or prognosis of CRC.