Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells

Abstract

Abstract We aimed to explore the role of circular RNA 0043256 (circ_0043256) in gastric cancer (GC) and its underlying mechanisms. The impact of circ_0043256 silencing on the proliferation, migration, apoptosis, and aerobic glycolysis of MKN-45 and AGS cells induced by CoCl2 was assessed through the utilization of CCK-8, wound healing assay, flow cytometry, and metabolic analysis. The interaction between circ_0043256 and miR-593-5p, as well as the involvement of the miR-593-5p/RRM2 axis in gastric cancer, were confirmed via luciferase assay, Western blot, and bioinformatics analysis. We found that circ_0043256 was up-regulated in GC tissues and CoCl2-treated MKN-45 and AGS cells. Silencing of circ_0043256 reversed CoCl2-induced proliferation, migration, and aerobic glycolysis in MKN-45 and AGS cells. Additionally, circ_0043256 silencing enhanced cell apoptosis and G2/M phase cell cycle arrest in response to CoCl2 treatment. Furthermore, the miR-593-5p/RRM2 axis was identified as a regulatory mechanism for circ_0043256 function in GC. Silencing of circ_0043256 and miR-593-5p mimic co-transfection significantly inhibited CoCl2-induced cellular responses in MKN-45 and AGS cells. A glycolysis inhibitor 2-DG further enhanced the inhibitory effect of circ_0043256 silencing on aerobic glycolysis of CoCl2-induced MKN-45 and AGS cells. Additionally, the inhibition of circ_0043256 resulted in a reduction in tumor volume and the expression of proliferation marker proteins in nude mice. Moreover, the suppression of circ_0043256 led to an increase in miR-593-5p expression and a decrease in RRM2 expression, ultimately causing a decrease in glycolytic-related proteins associated with the glycolytic pathway. Targeting this axis may offer a novel therapeutic approach for treating GC.

Keywords

• Circ_0043256
• miR-593-5p
• RRM2
• Gastric cancer
• Aerobic glycolysis