| Background and purpose:Gastric cancer is one of the most common malignant tumors worldwide.It has the characteristics of high incidence rate and high mortality,which seriously threatens human life and health.Tumor invasion and metastasis are still the main factors leading to poor prognosis of gastric cancer.The in-depth study of its mechanism and the search for possible prevention and treatment targets are urgent problems to be solved in this field.Epithelial mesenchymal transition(EMT)plays a key role in the invasion of primary epithelial malignant tumor cells into adjacent normal tissues.It is one of the important processes of tumor metastasis,but its specific mechanism is not completely clear.A large body of evidence suggests that transforming growth factor-β1(TGF-β1)triggers EMT occurrence,and the specific mechanism remains to be further elucidated.Interferon-induced interferon-induced transmembrane protein 2(IFITM2),previous studies have focused on viral inhibition.Recent studies were found to be highly expressed in most tumors and are considered a oncogene.Currently,studies of IFITM2 in gastric cancer are rarely reported.The previous study of our group confirmed for the first time that IFITM2 plays an important role in regulating EMT formation to promoting gastric cancer invasion and metastasis by participating in IGF1/IGF1R/STAT3 signaling.EMT mediated by the TGF-1 signaling pathway is a classical pathological process of tumor cells undergoing invasion and metastasis,and it is unclear whether IFITM2 is involved in this pathway-mediated EMT.In this study,bioinformatics was first used to analyze IFITM2 expression,prognostic effects and possible signaling pathways in gastric cancer,IFITM2 expression was subsequently validated using gastric cancer cells and clinical tissue samples,And further discusses the biological function in the signaling pathway,and provides new ideas and theoretical basis for the molecular mechanism and development of gastric cancer and preclinical research.Methods:1.The expression of IFITM2,influence on prognosis and possible signaling pathways in gastric cancer were analyzed by bioinformatics methods.2.Differences in IFITM2 expression were verified in gastric cancer cell lines and normal gastric mucosal cells,clinical gastric cancer tissues,and adjacent cancerous normal tissue samples.3.The expression of IFITM2 and EMT-related markers was detected in MGC803 and MKN45 cell lines,when TGF-β1 and its specific inhibitor SB431542 were added for different times.4.After transient transfection of silencing IFITM2 expression in the MGC803,MKN45 cell lines,its effects on cell migration and invasion function were observed,and the effect of this process on the expression of EMT-related markers caused by TGF-1 was further analyzed.5.Further mechanistic studies were conducted to investigate the effect of the EMT classical signaling pathway,TGF-β1/Smad2/3,after the silencing of IFITM2 expression.Results:1.IFITM2 is highly expressed in gastric cancer and is significantly associated with its progression,poor survival,and immune invasion.2.TGF-β1 promotes IFITM2 expression and EMT formation.3.Silencing of IFITM2 suppresses the migration invasion function of tumor cells and attenuated EMT formation caused by TGF-β1.4.After the silencing of IFITM2 expression,the expression of p-Smad2 and p-Smad3 in the EMT classical signaling pathway(TGF-β1/Smad2/3)was significantly inhibited.Moreover,a positive correlation between IFITM2 and the protein expression of p-Smad2 was further confirmed in clinical gastric cancer tissue samples.Conclusion:1.IFITM2 is highly expressed in gastric cancer and is associated with the poor prognosis of patients.2.IFITM2 promotes the epithelial-mesenchymal transformation of gastric cancer by mediating TGF-β1/Smad2/3 signaling pathway. |
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