Effect of Smad3 depletion on gene expression in mesenchymal like bladder cancer cells
The poor prognosis of bladder cancer (BCa) is primarily attributed to the acquisition of invasive and metastatic capabilities by tumor cells through epithelial-mesenchymal transition (EMT), yet the dynamic alterations in ferroptosis during EMT and their regulatory mechanisms remain unelucidated. Our research has revealed that in TGF-\u03b21-induced mesenchymal-like bladder cancer cells, ferroptosis-related genes (GPX4, SLC7A11) were markedly elevated, alongside increased lipid peroxides (LPO) and glutathione (GSH) levels. However, mesenchymal-like bladder cancer cells exhibited marked ferroptosis upon Smad3 knockdown, as evidenced by increased reactive oxygen species (ROS) levels, elevated lipid peroxide (LPO) and malondialdehyde (MDA) contents, and reduced glutathione (GSH) levels. These findings reveal the crucial regulatory role of SMAD3 in mesenchymal-like bladder cancer cells. To further investigate the underlying mechanism, we performed transcriptome analysis on mesenchymal-like bladder cancer cells following Smad3 knockdown to elucidate the core mechanism by which SMAD3 regulates ferroptosis