Upregulation of CircXPO1 Promotes the Progression of Gastric Cancer and May Serve as a Potential Auxiliary Biomarker for Its Diagnosis

Gastric cancer (GC) has a high incidence in China. There is a closed-loop structure in circRNAs, which is involved in various cellular biological processes such as tumor development. However, there is a lack of research on the function of circRNAs in GC. In this study, we aimed to explore the potential of circXPO1 as a diagnostic biomarker and the role of circXPO1 in the progression of GC. We screened out circXPO1 through circRNA sequencing. Using exonuclease digestion assay, agarose gel electrophoresis (AGE), Sanger sequencing, and gDNA experiment, we proved that circXPO1 contained a cyclic structure. Quantitative real-time fluorescent Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of circXPO1 in plasma and GC tissues. The receiver operating characteristic curve (ROC curve) was established to evaluate the diagnostic efficacy of circXPO1. The role of circXPO1 was assessed in vitro. The binding sites between circXPO1 and miRNAs were predicted by CircBank, Circinteractome, CircAtlas and miRanda databases. CircXPO1 was up-regulated in 67 GC tissues compared with the adjacent normal tissues (p = 0.0002). It was stable and hard to be degraded, which made it an ideal tumor biomarker. Compared with the patients in the normal control group, the expression level of circXPO1 in plasma was higher in GC patients (p < 0.001) and those with benign lesions (p = 0.0031) with statistically significant differences. CircXPO1 was proved to have satisfactory diagnostic efficacy in distinguishing GC patients from healthy donors (AUC = 0.813, 95% CI: 0.749-0.877). Besides, the diagnostic efficacy, sensitivity, and specificity could achieve 0.853, 78% and 86%, respectively, when circXPO1, CEA and CA199 were used together in diagnosis. In addition, in vitro experiments indicated that circXPO1 knockdown significantly weakened the proliferation, invasion and migration of GC cells. It was also predicted that circXPO1 could serve as a sponge of miR-1248 to regulate the progression of GC.