The Role And Molecular Mechanism Of CircGSE1 In Gastric Cancer

Background: Cancer of the stomach is the third most common malignant tumor in the world,with an estimated death toll of more than 782000 in 2018.Due to the lack of obvious symptoms and screening procedures,most patients were found to have advanced cancer at the first diagnosis.Therefore,it is urgent to further explore the molecular mechanism of cancer occurrence in order to formulate more effective treatment strategies.Cyclic RNA is a kind of neglected endogenous non-coding RNA in eukaryotic cells.They are usually composed of exons and are characterized by covalently closed continuous rings and typical splicing sites.New research shows that cyclic RNA is usually stable,conservative and low expression,and their expression levels vary between different cell types and tissue types.Circular RNA has many functions,including acting as micro RNA sponge,binding RNA binding protein(RBPS)and protein translation.In addition,cyclic RNA can affect the occurrence and development of many kinds of cancer,and affect many biological processes including proliferation,invasion and metastasis.Yet,the role and function of circ RNA in GC have not been fully elucidated.GSE1 protein(Genetic suppressor element 1),also known as KIAA0182,is a proline-rich protein.Previous studies demonstrated GSE1 promoted trastuzumab resistance in HER2-positive gastric cancer cells by regulating BCL-2expression,and in HER2-positive gastric cancer patients,high levels of GSE1 were associated with a higher risk of tumor lymph node metastasis and higher clinical stage.In addition,GSE1 can also enhance the proliferation,migration and invasion of gastric cancer cells through positive regulation of SLC7A5,and high expression of GSE1 often predicts poor prognosis in patients with gastric cancer.Objective: To investigate the function and potential molecular mechanism of GSE1-related circrnas in GC occurrence and progression.Methods: circ GSE1 is present as a circular RNA in the GC cell lines.We are in Significant higher circ GSE1 expression was observed in SGC-7901 cell lines,and significantly lower circ GSE1 expression was observed in MGC-803 and GES-1 cell lines.When circ GSE1 performed the in vitro functional assay,the overexpression of circ GSE1 significantly promoted the proliferation,migration,and invasion of GC cell lines in vitro.By micro RNA with predicted circ GSE1 binding in circ Interactome,TSCD,and circ Bank sites.The predicted micro RNA was screened by RT-q PCR and statistical analysis revealed that circ GSE1 was combined with hsa-mi R-661,meanwhile,our RNA pull-down assay verified this.We detected that hsa-mi R-661 could inhibit the proliferation,migration,and invasion process of GC cell lines by an in vitro functional assay.Through Targetscan,mi RDB,mi RWalk and mi RPath DB,we predicted hsa-mi R-661 potential target genes,hsa-mi R-661 was negatively correlated with DDA 1,and DDA 1 could promote the proliferation,migration and invasion process of GC cell lines by in vitro functional assay.Mechanistic analysis indicates that circ GSE1,as a "ce RNA" of hsa-mi R-661,alleviates the inhibitory effect of hsa-mi R-661 on its target gene DDA 1,and subsequently promotes tumorigenesis in GC.Results: We explored the role of circ GSE1 in GC cells.circ GSE1 In the GC cells Medium upregulation,promoting the proliferation and migration of GC cells,and combined with hsa-mi R-661,ultimately regulating the tumorigenesis and progression of GC cells.circ GSE1 Promote GC progression as a tumor cancer-promoting factor through the hsa-mi R-661 /DDA 1 axis,providing available biomarkers and therapeutic targets for GC patients.Conclusion: We explored the role of circ GSE1 in GC cells.circ GSE1 is up-regulated in GC cells,promoting the proliferation and migration of GC cells,and binding with hsa-mi R-661,ultimately regulating the tumorigenesis and progression of GC cells.We will further explore the mechanism of circ GSE1 in GC cells and tissues.