KAT7 Suppresses Tumorigenesis in Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating Cell Cycle and Ferroptosis Sensitivity.

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.

Targeted Restoration of GPX3 Attenuates Renal Ischemia/Reperfusion Injury by Balancing Selenoprotein Expression and Inhibiting ROS-mediated Mitochondrial Apoptosis.

BACKGROUND: Renal ischemia/reperfusion (IR) injury is the leading cause of acute kidney injury in both autologous and transplanted kidneys. Low-level glutathione peroxidase 3 (GPX3) is associated with renal IR injury. The exact mechanism of targeted GPX3 restoration in renal IR injury has yet to be determined. METHODS: The distribution of GPX3 in different tissues and organs of the body was investigated. The level of GPX3 in renal IR injury was assessed. To confirm the action of GPX3 and its mechanisms, IR models were used to introduce adeno-associated virus 9 containing GPX3, as well as hypoxia/reoxygenation-exposed normal rat kidney cells that consistently overexpressed GPX3. Reverse molecular docking was used to confirm whether GPX3 was a target of ebselen. RESULTS: GPX3 is abundant in the kidneys and decreases in expression during renal IR injury. GPX3 overexpression reduced renal IR injury and protected tubular epithelial cells from apoptosis. Proteomics analysis revealed a strong link between GPX3 and mitochondrial signaling, cellular redox state, and different expression patterns of selenoproteins. GPX3 inhibited reactive oxygen species-induced mitochondrial apoptosis and balanced the disordered expression of selenoproteins. GPX3 was identified as a stable selenoprotein that interacts with ebselen. Ebselen enhanced the level of GPX3 and reduced IR-induced mitochondrial damage and renal dysfunction. CONCLUSIONS: Targeted restoration of GPX3 attenuates renal IR injury by balancing selenoprotein expression and inhibiting reactive oxygen species-mediated mitochondrial apoptosis, indicating that GPX3 could be a potential therapeutic target for renal IR injury.