circRPS19 affects HK2-mediated aerobic glycolysis and cell viability via the miR-125a-5p/USP7 pathway in gastric cancer

Despite advances in diagnosis and treatment, gastric cancer (GC) remains a refractory disease, which limits overall survival. Therefore, it is key to identify novel targets to develop more effective and precise treatment. Circular RNAs (circRNAs) serve essential roles in the process of various human cancers. Through analyzing GSE83521 dataset, the present study identified a novel circRNA derived from ribosomal protein S19 (circRPS19), which was considered a potential treatment target for GC. Results of RT-qPCR indicated that circRPS19 was upregulated in GC compared with normal gastric epithelial cells. Loss-of function assays revealed that silencing of circRPS19 suppressed proliferation and aerobic glycolysis but increased apoptosis of GC cells. circRPS19 upregulated ubiquitin-specific processing protease 7 (USP7) expression by sponging microRNA (miR)-125a-5p. circRPS19 stabilized hexokinase 2 (HK2) protein by USP7-mediated deubiquitination of HK2. In vivo experiments confirmed that circRPS19 promoted GC progression and aerobic glycolysis. Taken together, circRPS19 induced aerobic glycolysis of GC cells by stabilizing HK2 protein via the miR-125a-5p/USP7 axis and thus promoting the progression of GC. These findings suggested that circRPS19 served a critical role in the progression of GC and may be a novel therapeutic target for GC.