Circ_0110805 Knockdown Enhances Cisplatin Sensitivity and Inhibits Gastric Cancer Progression by miR-299-3p/ENDOPDI Axis

Abstract

Xi Yang,1 Qunxiong Zhang,1 Bugao Guan2 1Digestive Department, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China; 2Department of General Surgery, People’s Hospital of Jinhu, Huaian, Jiangsu, People’s Republic of ChinaCorrespondence: Bugao GuanDepartment of General Surgery, People’s Hospital of Jinhu, 160 Shenhua Avenue, Jinhu, Huaian, Jiangsu, People’s Republic of ChinaEmail [email protected]: Gastric cancer is a prevalent primary stomach tumor. Cisplatin is frequently used to treat gastric cancer. However, the resistance of cisplatin in gastric cancer often occurs, which brings a heavy burden to gastric cancer treatment.Methods: In this study, we revealed a novel underlying mechanism about cisplatin-resistant effect in gastric cancer. A Cell Counting Kit-8 (CCK-8) cell viability assay and a xenograft model were performed to evaluate the function of circRNA in the cisplatin resistance of gastric cancer.Results: Compared with control groups, we observed that circ_0110805 was highly expressed, the mRNA and protein expression levels of ENDOPDI were dramatically upregulated, and the expression of miR-299-3p was significantly downregulated in gastric cancer cells, cisplatin-resistant gastric cancer tissues or cells. Functionally, circ_0110805 knockdown improved cisplatin sensitivity, induced cell apoptosis, whereas repressed cell viability, migration and invasion in AGS/DDP and HGC-27/DDP cells, which was reversed by miR-299-3p inhibitor. Additionally, ENDOPDI overexpression hindered the effects of miR-299-3p on cisplatin sensitivity and gastric cancer progression. Circ_0110805 knockdown enhanced cisplatin sensitivity in vivo. Mechanistically, circ_0110805 acted as a sponge of miR-299-3p and its targeted ENDOPDI.Conclusion: We showed that circ_0110805 knockdown increased the sensitivity of gastric cancer to cisplatin, which also repressed gastric cancer progression by sponging miR-299-3p to downregulate ENDOPDI expression. It might provide a new insight for future studying cisplatin-resistant gastric cancer.Keywords: cisplatin, sensitivity, circ_0110805, miR-299-3p, ENDOPDI, gastric cancer

Keywords

• cisplatin
• sensitivity
• circ_0110805
• mir-299-3p
• endopdi
• gastric cancer