Study Of The Molecular Mechanisms Study Of CircYAP1 On Growth Of Gastric Carcinoma Mediated By Toosendanin

BackgroundGC is one of the common malignant tumors in the digestive system,GC patients had a poor prognosis becuase of its hidden onset.In recent years,studies have found that circular RNA plays an important role in the occurrence and development of tumors.Our previous study had found that circYAP1 was lowly expressed in GC tissues,and TSN had an effective anti-gastric cancer effect.Therefore,this study investigated the expression level of circYAP1 in GC tissues and observed its effects on the biological behavior of GC cells.Furthermore,the mechanism of circYAP1 in GC cells and the molecular mechanism of TSN regulating the proliferation and invasion of GC cells were studied.Methods1.CircYAP1 was screened by CircNet,and its expression was detected in GC tissues and GC tissue microarrays by qPCR and FISH.The correlation of the expression of circYAP1 and clinicopathological characteristics with GC patients were analyzed.2.CircYAP1 was predicted to bind to miR-367-5p by CircNet and Circular RNA Interactome,and this was verified by circRIP assay and co-localization of circular RNA and miRNA assay.3.The effects of circYAP1 overexpression or knockdown on the biological behavior of GC cells were verified by CCK-8,EdU,clone formation,Transwell and cell rescue assay.4.P27^Kip1 was predicted to be the target gene of miR-367-5p by Targetscan,and the relationship between miR-367-5p and P27^Kip1 was verified by luciferase,and its expression was confirmed by WB.4.GC cells with circYAP1 knockdown were treated with TSN,and the effect of TSN on proliferation and invasion of GC cells was verified.Results:1.By qPCR and FISH assay,we found that the expression of circYAP1 was lower in GC tissues than in adjacent tissues.The expression of circYAP1was positively correlated with the prognosis of GC patients.Multivariate Cox regression model analysis showed that circYAP1 was an independent prognostic factor for survival of GC patients.2.Overexpression of circYAP1 inhibited GC cell proliferation,invasion in vitro,and inhibited tumor growth in vivo.Knockdown of circYAP1promoted GC cell proliferation,invasion in vitro.Functional analysis showed that circYAP1 regulated P27^Kip1 expression by sponging miR-367-5p.3.The effects of circYAP1 knockdown on proliferation and invasion of GC cells could be inhibited by TSN,which may be related to the upregulation of circYAP1 expression by TSN.Conclusion:CircYAP1 has a low expression level in GC tissues and is an independent factor for the prognosis of gastric cancer patients.CircYAP1 inhibits the proliferation and invasion of GC cells.CircYAP1 regulates the biological behavior of gastric cancer cells by absorbing miR-367-5p and regulates the expresion of P27^Kip1.Toosendanin inhibits the proliferation and invasion of GC cells may partly by upregulating the expression of circYAP1 and P27^Kip1.