Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression

Long noncoding RNA umthelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remain elusive. We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins (RBPs) with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and proliferation of BLCA. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2), an enzyme transferring glutamate to alpha-ketoglutarate, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1 and hnRNP I/L on metabolism and proliferation via glutamine-driven anaplemsis in BLCA. Our study revealed the critical role of UCA1-mediated mechanisms involved in glutamine-driven anaplerosis and provided novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.

Automated summary

The long noncoding RNA UCA1 plays a critical role in metabolic reprogramming in bladder cancer. It binds to heterogeneous nuclear ribonucleoproteins I and L and affects glycolysis, TCA cycle, glutaminolysis, and proliferation in bladder cancer. Additionally, UCA1 regulates glutamine-driven anaplerosis and enhances tumor cell metabolism.