Inhibition of circRNA circVPS33B reduces cell malignant behaviors and Warburg effect through regulation of the miR-873-5p/HNRNPK axis in infiltrative gastric cancer [post]

Yizhuo Lu, Jia Cheng, Wangyu Cai, Huiqin Zhuo, Guoyang Wu, Jianchun Cai
2020 unpublished
Background Circular RNA VPS33B (circVPS33B) is upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct. Methods Expression of circVPS33B, miR-873-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, colony formation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by
more » ... yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound healing, or transwell assays. Several protein levels were examined by western blotting. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of XGC-1 cells were evaluated by XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The relationship between circVPS33B or HNRNPK and miR-873-5p was verified by dual-luciferase reporter and/or RNA pull-down assays. In vivo tumorigenesis assay was executed for verifying the in vitro results. Results CircVPS33B and HNRNPK were upregulated while miR-873-5p was downregulated in infiltrative GC tissues and XGC-1 cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, colony formation, migration, invasion, and Warburg effect of XGC-1 cells in vitro. CircVPS33B regulated HNRNPK expression via sponging miR-873-5p. The inhibitory influence of circVPS33B knockdown on the malignancy and Warburg effect of XGC-1 cells was overturned by miR-873-5p inhibitor. HNRNPK overexpression reversed the repression of the malignancy and Warburg effect of XGC-1 cells caused by miR-873-5p mimic. Conclusions CircVPS33B accelerated infiltrative GC progression through regulating the miR-873-5p/HNRNPK axis, manifesting that circVPS33B might be a promising target for infiltrative GC treatment.
doi:10.21203/rs.3.rs-43509/v1 fatcat:nheekyidtrbtjak5oeqzftwoki