Hypoxia-induced circular RNA has_circRNA_403658 promotes bladder cancer cell growth through activation of LDHA.

Bladder cancer (BC) is one of the most common cancers in male patients, and the leading cause of cancer-related death in men. Hypoxia plays a critical role in carcinoma biology, including in bladder cancer. However, whether circular RNAs are associated with hypoxia-mediated progression of bladder cancer remain unknown. In this study, our aim was to investigate the role of circular RNA on the hypoxic adaptive response in bladder cancer. Here, we identified a hypoxia-inducible circular RNA, has-circRNA-403658 that contributes to bladder cancer progression. Has-circRNA-403658 is spliced from its host gene, ZNF292, through back-splicing between the 1st and 4th exon. We demonstrated that has-circRNA-403658 was an important circRNA that upregulated in bladder cancer cells under hypoxia, and higher has-circRNA-403658 levels were associated with poorer survival outcome. Silencing has-circRNA-403658 in bladder cancer cells inhibited cell growth and induced cell apoptosis. In addition, has-circRNA-403658 was induced by HIF1α and silencing has-circRNA-403658 inhibited LDHA-mediated aerobic glycolysis, inhibiting bladder cancer cell growth. Thus, our results suggest that has-circRNA-403658 may function as a novel therapeutic target in human bladder cancer.