Circ_0000235 Targets MCT4 to Promote Glycolysis and Progression of Bladder Cancer by Sponging miR-330-5p
Warburg effect plays a crucial role in bladder cancer (Bca) development. However, the mechanism by which glycolysis is involved in Bca remains poorly understood. CircRNAs commonly play a regulatory role in tumor progression. Our study discovered and identified a novel circRNA, hsa_circ_0000235 (circ235), and investigated its role in the glycolytic process, which further results in the progression of Bca. We applied qRT-PCR to assess its clinicopathological relevance and evaluated its proliferation, migration, and glycolytic capacity. We investigated its mechanism using RNA immunoprecipitation, dual-luciferase reporters, and fluorescence in situ hybridization. The findings demonstrated that circ235 was dramatically increased in Bca tissues and was related to a worse prognosis. In vitro studies revealed that circ235 accelerated the rate of extracellular acidification and promoted glucose uptake and lactate manufacture in Bca cells. Additionally, it strengthened the capacity of Bca cells to proliferate and migrate. Experiments on animals revealed that downregulating circ235 dramatically reduced carcinogenesis and tumor growth.  Cir235 activates monocarboxylate transporter 4 (MCT4) by sponging miR-330-5p, which promotes glycolysis and tumor growth. In conclusion, these findings imply that circ235 may be a viable molecular marker and therapeutic site for Bca. Overall design: To investigate the downstream signaling pathways regulated by circ_0000235 in bladder cancer, we treated T24 cell line with siRNAs targeting two different targets and established two biological replicate samples.