FOXO3a/Parkin Regulates The Proliferation,Migration And Apoptosis Of Gastric Cancer Cells By Targeting ABCE1

Objective Gastric cancer is a malignant tumor found in the epithelium of the gastric mucosa,and its mortality rate ranks the second in the world.In recent years,significant progress has been made in the research of gastric cancer,but its early diagnosis and pathogenesis are still not fully understood.Parkin,an E3 ubiquitin ligase,has been shown to act as a tumor suppressor gene in a variety of cancers,including gastric cancer.However,the mechanisms of Parkin in cancers remain unclear.In this study,we will further explore the expression of Parkin in gastric cancer tissues,the role and mechanism of Parkin in the proliferation,migration and apoptosis of gastric cancer cells.Through the research of this project,we hope to propose new targets for the diagnosis and treatment of gastric cancer.Methods The expression levels of Parkin in gastric cancer tissue samples and gastric cancer cell lines were detected by real-time quantitative PCR and Western blot;apoptosis were detected by flow cytometry;cell viability was detected by MTT colorimetry;cell migration was detected by wound healing experiments and transwell experiments;construct the luciferase reporter gene carrier of the parkin gene promoter,and test the luciferase activity to verify the combination of FOXO3 a and Parkin gene promoter;the binding of Parkin to the ATP binding cassette transporter E1(ABCE1)was verified by co-immunoprecipitation experiment.Results In this study,we found that Parkin was downregulated in grastic cancer tissues and gastric cancer cell lines.When Parkin is overexpressed,it can inhibit the proliferation and migration and promote the apoptosis of gastric cancer cells.When treated with doxorubicin(DOX),Parkin expression was up-regulated,which promoted apoptosis.FOXO3 a can inhibit the proliferation,metastasis and promote apoptosis of gastric cancer cells by regulating the expression of Parkin at the transcriptional level.In addition,Parkin intercats with ABCE1,Parkin inhibits cell proliferation,metastasis and promotes apoptosis by negatively regulating the expression of ABCE1.Conclusion Our research found that parkin plays the role of tumor suppressor genein gastric cancer,inhibits the proliferation and migration of gastric cancer cells,and promotes apoptosis.We also revealed that FOXO3a-Parkin-ABCE1,a new signaling pathway,is involved in the development of gastric cancer.These regulatory molecules may serve as potential therapeutic targets for gastric cancer.