The integration of transcriptomics and metabolomics elucidates the antitumor mechanisms of mycophenolic acid in bladder cancer cells

The potential Anticancer effects of mycophenolic acid (MPA), an inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor, and its ability to prolong survival have been suggested. However, the comprehensive impact of MPA on bladder Cancer remains unclear. Our results demonstrate that MPA induces both Ferroptosis and Apoptosis in human bladder Cancer cells. To investigate the underlying mechanisms, we employed integrated transcriptomic and metabolomic analyses. Our analysis revealed that differentially expressed genes (DEGs) are primarily implicated in the regulation of metabolism, inflammatory responses, and angiogenesis. Metabolomic profiling identified phosphocreatine, 2'-CMP, CDP, and Others as differentially accumulated metabolites (DAMs). Integrated analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) demonstrated that MPA significantly alters the metabolism of key compounds (GMP, phenol, glutathione, NAD+, cytosine) and regulates critical genes (tyrosine, LDHA, LDHB). Notably, the dysregulation of genes and metabolites associated with Reactive Oxygen Species (ROS)-related pathways may serve as a central mechanism by which MPA facilitates Ferroptosis and Apoptosis in bladder Cancer.

Apoptosis; Bladder cancer; Ferroptosis; IMPDH; Mycophenolic acid.