IPO5 Mediates EMT And Promotes Esophageal Cancer Development Through The RAS-ERK Pathway

ObjectiveIn the development of many tumors,IPO5,as a member of the nuclear transporter family,exerts a significant function.By studying IPO5 expression in esophageal cancer tissues,the mechanism associated with IPO5 improving esophageal cancer development was explored in this study.MethodsIn this study,bioinformatics database was used to comprehensively analyze esophageal cancer tissue and normal esophageal tissue to obtain differentially expressed genes,screen differentially expressed gene IPO5,and evaluate the prognosis of patients with esophageal cancer by Kaplan-Meier method.We took specimens of esophageal cancer from patients and detected the expression of IPO5 in tumor and normal tissues by immunohistochemistry.The IPO5 gene-silenced esophageal cancer cell model was constructed by lentivirus transfection.Through the Transwell invasion assay,CCK-8 assay,and cell scratch assay,this study investigated the effects of IPO5 on cell propagation,invasion,and transfer.What is more,we identified the influences of IPO5 on the cell cycle through flow cytometry and established a subcutaneous tumor-forming model in nude mice.Immunohistochemistry was used to verify the expression of KI-67,and this study detected the modifications of cell pathway-related proteins using Western blot and applied EMT-related proteins to explain the mechanism of esophageal cancer induced by IPO5.ResultsAccording to database survival analysis,IPO5 high-expression patients had shorter disease-free survival than IPO5 low-expression patients.Compared to normal tissues,the IPO5 expression in cancer tissues was significantly higher in clinical trials(P<0.05).After knocking out IPO5 gene expression,cell proliferation capacity and invasion capacity were reduced(P<0.05)and decreased(P<0.01)in the IPO5-interfered group rather than the negative control group.The growth cycle of esophageal carcinoma cells was arrested in the G2/M phase after IPO5 gene silencing(P<0.01).Tumor-forming experiments in nude mice confirmed that after IPO5 deletion,the tumor shrank,the expression of KI67 decreased,the downstream protein expression level of the RAS-ERK pathway decreased after sh-IPO5 interference(P<0.01),and the level of EMT marker delined(P<0.05).ConclusionIn esophageal cancer,IPO5 is highly expressed and correlates with survival rate.Esophageal cancer cell growth and migration were significantly affected by the inhibition of IPO5 in vitro and in vivo.IPO5 mediates EMT using the RAS-ERK signaling pathway activation and promotes esophageal cancer cell development in vivo and in vitro.