Targeting PGC-1α in Bladder Cancer: Unraveling Energy Metabolism Reprogramming for Therapeutic Intervention

ABSTRACT: Metastatic bladder cancer is a malignant tumor with high metastatic potential. The etiology and molecular mechanism are still not fully understood. This study aimed to investigate the effect of PGC-1 α siRNA delivered by liposomal nanoparticles on bladder cancer cells, in order to reveal its mechanism in tumor cell reprogramming and energy metabolism regulation. Through transcriptome, proteome and metabolomics, we found that PGC-1 α was significantly upregulated in bladder cancer metastasis, and constructed a nanoparticle delivery system for efficient delivery of PGC-1 α siRNA. In vitro results showed that PGC-1 α silencing inhibited mitochondrial biogenesis and energy metabolism in bladder cancer cells, and interfered with the extranuclear transport of mRNA. Metabolomic analysis further confirmed the changes in cellular metabolism, especially the effects of glycolysis and tricarboxylic acid cycle pathways. The in vivo model further verified that si-pgc-1 α LNP could significantly reduce the number of lung metastases of metastatic bladder cancer, showing anti metastatic potential. These findings reveal the important role of PGC-1 α in the regulation of energy metabolism and metastasis of bladder cancer cells, and provide a new strategic direction for the treatment of metastatic bladder cancer.

ORGANISM(S): Mus Musculus

SUBMITTER: Hao Zhang  

PROVIDER: PXD062153 | iProX | Sat Mar 22 00:00:00 GMT 2025

REPOSITORIES: iProX