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Abnormal expression of TBL1XR1 in pancreatic ductal adenocarcinoma and its clinical significanceObjective:To investigate the expression of transduction protein ?-like 1X-related protein 1(TBL1XR1)in pancreatic ductal adenocarcinoma and its relationship with clinicopathological features of pancreatic ductal adenocarcinoma.Methods:A total of 46 cases of pancreatic ductal adenocarcinoma tumors and their matched paracancerous tissues were collected from the First People's Hospital of Changshu City,Jiangsu Province.Immunohistochemistry(IHC)staining,Western Blot and real-time fluorescence quantification were used.The expression level of TBL1XR1 was detected by PCR,and the correlation was analyzed by combining clinical pathological data.The study was approved by the ethics committee of the hospital,and all patients were informed in advance and signed informed consent.Results:46 patients with pancreatic ductal adenocarcinoma were treated with tumor tissue and paracancerous tissues.TBL1XR1 was highly expressed at mRNA transcription level and protein translation level,and the difference was statistically significant(p<0.05).Among the 46 patients,27 patients were over 60 years old,including 68.4%positive for TBL1XR1 and 19 patients younger than 60 years old,of which 66.7%were positive for TBL1XR1,p>0.05,no statistical significance.There were 23 male patients,including 65.2%of TBL1XR1 positive,and 23 females,of which TBL1XR1 was 69.6%positive,p>0.05,no statistical significance.In the characteristics of pancreatic ductal adenocarcinoma,the number of patients with tumor diameter>3 cm was 12,of which TBLlXRl was positive 50.0%,and the number of patients with tumor diameter<3 cm was 34,of which TBL1XR1 was 73.5%positive,p>0.05,no statistics.Learning meaning.Among the tumor TNM stages,8 patients in stage ?-?,including TBS1XR1 positive 25.0%,? patients 38 cases,of which TBL1XR1 positive 76.3%,p<0.01,statistically significant.In the case of local lymph node metastasis,19 patients with lymph node metastasis in 46 patients,including TBL1XR1 positive 73.7%,no lymph node metastasis 27 cases,of which TBL1XR1 positive 63.0%,p>0.05,no statistical significance.In conclusion,there was no significant correlation between the expression level of TBL1XR1 in PDAC and the age,sex,tumor differentiation,tumor size(maximum diameter)and location,and lymph node metastasis(p>0.05).However,it was closely related to tumor malignancy and TNM staging(p<0.01),which was statistically significant.Patients with PDAC had a high degree of malignancy,and their TBL1XR1 expression was significantly higher than that of low-grade PDAC patients(75.6%vs 33.3%).Conclusion:1.TBL1XR1 is highly expressed in pancreatic ductal adenocarcinoma.2,TBL1XR1 and PDAC tumor malignancy(TNM staging)are closely related.3.High expression of TBL1XR1 suggests that patients have poor prognosis and low survival rate,suggesting that TBL1XR1 gene may play an important role in the progression of pancreatic cancer.Part ? TBL1XR1 regulates proliferation,apoptosis and tumorigenic ability of pancreatic cancer cells in vitro and in vivoObjective:To investigate the regulation of TBL1XR1 on proliferation,apoptosis and tumorigenic ability of pancreatic cancer cells in vitro and in vivo.Methods:The expression of TBLXR1 protein in pancreatic cancer cell lines with high basal expression was reduced by RNA interference.The interference silencing efficiency was verified by qRT-PCR and Western Blot after 48-72 hours of transfection.,clone formation assay,cell cycle assay,apoptosis assay and tumor formation assay in nude mice to observe the effect of TBL1XR1 expression on proliferation and tumor cell apoptosis of human pancreatic cancer cells in vitro and in vivo.Low cell lines were transfected with cytoplasmic DNA to investigate the effects on cell function.Low expression of cellular plasmid DNA transfection cell lines,was used to study effects on cell function.Results:The expression levels of TBL1XR1 in pancreatic cancer cell lines were different,with relatively high levels of expression in the Aspc-1 and Pane1 cell lines.The efficiency of high level silencing of TBL1XR1 was obtained using RNAi technology for these two cell lines.TBL1XR1 promotes proliferation and clonal formation of pancreatic cancer cells in vitro.TBL1XR1 affects the cycle progression of pancreatic cancer cells and promotes cell transformation to G2/M phase.TBL1XR1 inhibits apoptosis in pancreatic cancer cells.TBL1XR1 promotes tumor formation and proliferation of pancreatic cancer cells in nude mice.By DNA transfection cell lines to express exogenous TBL1XR1 increased obviously.Conclusion:TBL1XR1 can promote the proliferation and clonality of pancreatic cancer cells in vitro.TBL1XR1 may promote cell survival by reducing G0/1 phase arrest and inhibiting apoptosis of pancreatic cancer cell lines.TBL1XR1 plays a role in tumor growth in pancreatic cancer cells.Important role.Part ? TBL1XR1 promotes the development of pancreatic ductal adenocarcinoma by activating PI3K signaling pathwayObjective:To investigate the effects of TBL1XR1 on the proliferation and apoptosis of pancreatic cancer cells.Methods:Western Blot assay was used to verify the expression of cell cycle-related proteins,the expression of apoptosis-related proteins,and the phosphorylation levels of PI3K,AKT and ERK1/2 signaling pathways in pancreatic cancer cells after RNAi interference with TBL1XR1 expression.PI3K pathway inhibitor LY294002 was used to observe whether it could restore the proliferation of pancreatic cancer cells.Results:After the expression of TBL1XR1 was decreased,the expression of Cyclin A and CDK2 cyclin decreased,the expression of Cyclin D cyclin increased,and the expression of csc25a cyclin also decreased.Insufficient TBLlXR1 protein levels result in the retention of pancreatic cancer cells in the G0/1 phase,and the cells fail to progress smoothly from the G0/1 phase to the S phase and subsequent G2/M phase.After the expression of TBL1XR1 decreased,the expression of Bax increased,Bcl-2 decreased,and the ratio of Bax/Bcl-2 increased,which represented the promotion of apoptosis.In addition,after decreasing the expression level of TBL1XR1 protein,the phosphorylated form of PI3K expression decreased,and the phosphorylated form of Akt expression also decreased,indicating that the PI3K/Akt pathway signal transduction activity decreased,that is,its ability to promote pancreatic cancer cell proliferation was weakened.PI3K pathway inhibitor LY294002 can effectively restore the role of TBL1XR1 in promoting the proliferation of pancreatic cancer cells.Conclusion:The expression of cell cycle-associated protein and apoptosis-related protein in TBL1XR1 is consistent with the phenotypic results of pancreatic cancer cells.TBL1XR1 plays a role in promoting the proliferation of pancreatic cancer cells by activating the PI3K/Akt signal transduction pathway in pancreatic cancer cells.The PI3K/Akt pathway is the major downstream pathway for TBL1XR1 to exert its biological function.The PI3K inhibitor LY294002 can effectively restore the effect of TBL1XR1 on the proliferation of pancreatic cancer cells. |
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