Mitochondria-located circRCP regulates redox homeostasis via stabilizing LRPPRC/SLIRP complex to promote bladder urothelial carcinoma tumorigenesis.

The function of circular RNAs (circRNAs) located within the mitochondria in the pathogenesis of urothelial carcinoma of the bladder (UCB) remains largely unexplored. This study identified a mitochondria-located circRNA named circRCP from the nuclear genome of UCB cells. It is frequently upregulated in UCB and serves as an independent prognostic factor. This study further illustrates that circRCP enhances UCB tumorigenesis by regulating intracellular redox homeostasis. The knockdown of circRCP heightens mitochondrial oxidative stress, which leads to ROS generation, consequently triggering UCB cell apoptosis. Mechanistically, by forming a circRCP/LRPPRC/SLIRP RNA-protein ternary complex, circRCP enhances the LRPPRC/SLIRP stability and protects LRPPRC from ubiquitination and proteasomal degradation. Clinically, UCBs exhibiting high circRCP and LRPPRC expression had the worst outcomes. Taken together, we have identified a mitochondria-located circRNA that protects UCB cells from oxidative stress, highlighting its potential role in UCB pathogenesis and warranting further investigation into its therapeutic applicability.