OncoTargets and Therapy (May 2021)
Inhibition of circRNA circVPS33B Reduces Warburg Effect and Tumor Growth Through Regulating the miR-873-5p/HNRNPK Axis in Infiltrative Gastric Cancer
Abstract
Yizhuo Lu,1 Jia Cheng,2 Wangyu Cai,2 Huiqin Zhuo,2 Guoyang Wu,1 Jianchun Cai2 1Department of General Surgery, Zhongshan Hospital Xiamen University, Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, 361004, People’s Republic of China; 2Department of Gastrointestinal Surgery, Zhongshan Hospital Xiamen University, Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, 361004, People’s Republic of ChinaCorrespondence: Jianchun CaiDepartment of Gastrointestinal Surgery, Zhongshan Hospital Xiamen University, Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Room 203, No. 146, Hubin South Road, Siming District, Xiamen, Fujian Province, 361004, People’s Republic of ChinaTel +86 592-2993191Email [email protected]: Circular RNA VPS33B (circVPS33B) has been revealed to be upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct.Methods: Expression of circVPS33B was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound-healing, or transwell assays. Protein levels were detected by Western blotting. Measurements of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were executed using an XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The regulatory mechanism of circVPS33B had been explored by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. In vivo tumorigenesis assay was executed to verify the oncogenicity of circVPS33B.Results: CircVPS33B was upregulated in infiltrative GC tissues and cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, migration, invasion, EMT, and Warburg effect of infiltrative GC cells in vitro. Mechanically, circVPS33B regulated heterogeneous nuclear ribonucleoprotein K (HNRNPK) expression via sponging miR-873-5p. Furthermore, miR-873-5p inhibitor offset circVPS33B knockdown-mediated effects on malignant behaviors and Warburg effect of infiltrative GC cells. HNRNPK overexpression reversed the inhibitory impact of miR-873-5p mimic on malignant behaviors and Warburg effect of infiltrative GC cells.Conclusion: CircVPS33B accelerated Warburg effect and tumor growth through regulating the miR-873-5p/HNRNPK axis in infiltrative GC, manifesting that circVPS33B might be a potential target for infiltrative GC treatment.Keywords: circVPS33B, miR-873-5p, HNRNPK, infiltrative GC
