RESUMEN
Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive malignancies in the urological system, known for its high immunogenicity. However, its pathogenesis remains unclear. This study utilized bioinformatics algorithms and in vitro experiments to investigate the role of KAT7 in ccRCC. The results indicate that KAT7 is significantly downregulated in ccRCC tissues and cell lines, which is linked to distant metastasis and unfavorable outcomes in ccRCC patients. Overexpression of KAT7 in vitro notably decreased the proliferation, migration, and invasion of renal cancer cells and inhibited Epithelial-Mesenchymal Transition (EMT). Additionally, Gene Set Enrichment Analysis (GSEA) demonstrated that KAT7-related gene functions are associated with cell cycle and ferroptosis transcription factors. Treatment with a KAT7 acetylation inhibitor in ccRCC cell lines reversed the S phase arrest caused by KAT7 overexpression. Similarly, ferroptosis inhibitors alleviated ferroptosis induced by overexpressed KAT7. In conclusion, the findings suggest that KAT7 acts as a tumor suppressor in ccRCC by modulating the cell cycle and ferroptosis sensitivity, underscoring its potential as a therapeutic target and prognostic biomarker for renal cell carcinoma patients.
RESUMEN
Effects of selenoproteins on many renal diseases have been reported. However, their role in renal ischemia-reperfusion (I/R) injury is unclear. The present study was performed to investigate the impact of ebselen and renal I/R injury on the expression of selenoproteins. Sprague-Dawley rats were pretreated with or without ebselen (10 mg/kg) through a daily single oral administration from 3 days before renal I/R surgery. RT-qPCR (real-time quantitative PCR) was performed to determine the mRNA expression of 25 selenoprotein genes in the renal tissues. The expression levels of two selenoproteins, including GPX3 (glutathione peroxidase 3) and DIO1 (iodothyronine deiodinase 1), were evaluated by Western blot or/and IHF (immunohistofluorescence) assays. Furthermore, renal function, renal damage, oxidative stress, and apoptosis were assessed. The results showed that in renal I/R injury, the mRNA levels of 15 selenoprotein genes (GPX1, GPX3, GPX4, DIO1, DIO2, TXNRD2, TXNRD3, SEPHS2, MSRB1, SELENOF, SELENOK, SELENOO, SELENOP, SELENOS, and SELENOT) were decreased, whereas those of eight selenoprotein genes (GPX2, GPX6, DIO3, TXNRD1, SELENOH, SELENOM, SELENOV, and SELENOW) were increased. I/R also induced a reduction in the expression levels of GPX3 and DIO1 proteins. In addition, our results indicated that ebselen reversed the changes in those selenoprotein genes, excluding SELENOH, SELENOM, SELENOP, and SELENOT, in renal I/R injury and alleviated I/R-induced renal dysfunction, tissue damage, oxidative stress, and apoptosis. To our knowledge, this is the first study to investigate the changes of 25 mammalian selenoprotein genes in renal I/R injury kidneys. The present study also provided more evidence for the roles of ebselen against renal I/R injury.