SAP30 promotes clear cell renal cell carcinoma proliferation and inhibits apoptosis through the MT1G axis.

Sin3A-associated protein 30 (SAP30) is a crucial component of the SIN/HDAC histone deacetylase complex and acts as a scaffold that facilitates target gene binding. SAP30 is highly expressed in various tumours; however, its role in renal cell carcinoma (RCC) remains unclear. In our study, we observed the upregulation of SAP30 in clear cell renal cell carcinoma (ccRCC) tissues, and its elevated expression was correlated with a poor prognosis. Previous research has suggested that SAP30 may influence the growth, proliferation, and apoptosis of RCC cells. Gene Ontology (GO) analysis of the downstream regulatory targets of SAP30 revealed that SAP30 suppressed the expression of MT1G, a protein that binds to p53. Mechanistically, SAP30 inhibited MT1G transcription, thereby impairing the function of MT1G in delivering zinc ions to p53, which diminished p53 activity. Moreover, reduced MT1G levels attenuated the inhibitory effect of MT1G on MDM2, further destabilizing p53. Consequently, this cascade promoted RCC progression. In conclusion, our findings indicate that SAP30 inhibits the p53 pathway through MT1G suppression, suggesting that SAP30 and MT1G are potential prognostic markers and therapeutic targets for RCC.