| Objective:Gastric cancer is an malignant tumor that seriously threatens human life and health,the latest cancer statistics show that there are approximately1030,000 new cases of gastric cancer worldwide and almost 780,000 deaths each year.In recent years,with the promotion of multidisciplinary comprehensive treatment,the level of gastric cancer treatment has improved.However,the 5-years survival rate after radical resection of advanced gastric cancer still lingers at 30%-50% for a long time.Metastasis is the leading cause of death from advanced gastric cancer.Among them,peritoneal metastasis can cause a large number of complications such as refractory ascites and electrolyte imbalance.The existing treatment methods are very limited and cannot achieve a radical cure effect.Current studies have found the YAP1 is highly expressed in ascites cancer cells from patients with peritoneal metastasis.PLAU,also named Urokinase-type plasminogen activator(u PA),is performs as a protease and participate the transition of plasminogen to plasmin.Later studies have found that YAP1 may play a role by regulating PLAU,thereby promoting the occurrence of peritoneal metastasis of gastric cancer,but the specific mechanism remains to be explored.This study aims to explore the correlation between YAP1 and PLAU,provide new insights into the peritoneal metastasis,and provide a theoretical basis for development of drugs against gastric cancer peritoneal metastasis.Materials and methods: In this study,we downloaded the data sets of overexpressing YAP1 and knocking down YAP1 through the GEO database,and used R language to merge the data sets of overespressing YAP1.Paired t test used to calculate the genes that were significantly up-regulated after overexpression of YAP1 and those that were significantly down-regulated after YAP1 was knocked down.We collected x cases of ascites cells from patients with peritoneal metastasis.All samples were frozen in liquid nitrogen in half an hour after centrifugation.Immunohistochemistry were used to detect the content of cancer cells and the expression of YAP1 in ascites cells.PCR and WB were used to detect the expression of YAP1 and PLAU in gastric cancer cell lines.The IC50 experiment was used to detect the appropriate treatment concentration of YAP1 inhibitor.Inhibition or overexpression of YAP1 by inhibitors or lentiviruses,PCR and WB to detect the expression of PLAU,and explore the correlation between YAP1 and PLAU.Results: We get the key gene PLAU through the intersection of the database.Immunohischemical results showed that YAP1 was significantly high in ascites cells from patients with peritoneal metastasis.PCR and WB results showed that YAP1 was highly expressed in gastric cancer cell lines,including two ascites cell lines,SNU-16 and SNU-5.IC50 results showed that YAP1 inhibitors can significantly inhibit the proliferation of gastric cancer,and we determined the concentration of inhibitors.In addition,after we knocked down or overexpressed YAP1 with inhibitors and lentivirus,the results of PCR and WB showed that the expression of PLAU would change in the same direction as YAP1 changes,and there is a significant correlation between the two.Transwell invasion and migration experiments show that inhibiting YAP1 can significantly reduce the invasion and migration ability of gastric cancer cells.This situation may be achieved by regulating PLAU.Conclusion: YAP1 is highly expressed in ascites cells.PLAU is mainly expressed in the cytoplasm and is high in gastric cancer cell lines.YAP1 inhibitors can significantly inhibit the proliferation of gastric cancer,inhibit the expression of YAP1,and at the same time inhibit the expression of PLAU.YAP1 promotes the proliferation and invasion of gastric cancer cells,and may function by regulating PLAU.YAP1 is related to PLAU,and may regulate it to affect gastric cancer peritoneal metastasis. |
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