The Mechanism Of BAG2 Regulating Apoptosis Of Gastric Cancer Cells

Background: Gastric cancer is one of the most common malignant tumors of the digestive system.Due to its insidious onset,low early diagnosis rate and easy recurrence,its prognosis is poor.Therefore,better targets are needed to improve the specificity and accuracy of targeted therapy for gastric cancer.The Bcl-2-associated athanogene(BAG)protein family was originally thought to be a group of proteins that prevent cell death by interacting with Bcl-2.More and more studies have confirmed that BAG2 not only plays an important role in neurodegenerative diseases,but also participates in the regulation of various physiological activities such as apoptosis and tumorigenesis.However,the mechanism of BAG2 in gastric cancer has not been fully studied.Objective : BAG2 has been shown to be involved in tumor growth and metastasis as a co-chaperone,but its biological function in gastric cancer has not been fully studied.The purpose of this study is to explore the role of BAG2 in the apoptosis of gastric cancer cells and its potential mechanism,and to provide a theoretical basis for the treatment of gastric cancer by targeting BAG2.Methods: The results of bioinformatics analysis showed that: BAG2 was highly expressed in gastric cancer tissues,and at the same time,HSP70 was highly expressed in various malignant tumors,especially in gastric cancer,its expression in cancer tissues was significantly higher than its expression in paracancerous tissues.Moreover,in gastric cancer,there is a correlation between the expression of BAG2 and HSP70.After knocking out BAG2 in gastric cancer cell lines,the expression of HSP70 was significantly decreased;immunohistochemical experiments confirmed that the expression of BAG2 and HSP70 in gastric cancer tissues was higher than that in corresponding paracancerous tissues,and there were significant differences.The results of immunofluorescence and co-immunoprecipitation showed that BAG2 interacted with HSP70 protein and HSP70 and ubiquitinase 3CHIP(C terminus of Hsc70-interacting protein)/STUB1 protein,indicating that they were functionally related.The results of ubiquitination experiments showed that BAG2 can inhibit CHIPmediated ubiquitination of HSP70.Subsequent co-immunoprecipitation results showed that HSP70 also interacted with apoptosis-inducing factor(apoptotic protease activating factor-1,Apaf-1)protein and between Apaf-1 and cytochrome C(Cytc)protein.The results of Western Blot and flow cytometry showed that the ability of BAG2 to promote the proliferation of gastric cancer cells was weakened after knocking out HSP70,and the ability of BAG2 to inhibit the apoptosis of gastric cancer cells was weakened,indicating that BAG2 can be inhibited through the BAG2/CHIP/HSP70/Apaf-1/Cytc pathway Apoptosis of gastric cancer cells promotes the occurrence and development of gastric cancer.Conclusions:By inhibiting the ubiquitination degradation of HSP70 mediated by CHIP,BAG2 inhibits the classical apoptotic pathway,thereby inhibiting the apoptosis of gastric cancer cells and promoting the occurrence and development of gastric cancer.BAG2 is a potential specific target for the treatment of gastric cancer,which may provide new targets and ideas for the clinical diagnosis and treatment of gastric cancer.