SAP30 promotes clear cell renal cell carcinoma proliferation and inhibits apoptosis through the MT1G/P53 axis

Abstract

Abstract Sin3-associated polypeptide p30(SAP30) is an important component of the SIN/HDAC histone deacetylase complex that act as a scaffolding and facilitates target gene binding. SAP30 is highly expressed in a variety of tumors, however; its role in renal cell carcinoma is still unclear. In our study, we found that SAP30 was upregulated in tissues of renal clear cell carcinoma (ccRCC), and high SAP30 expression was associated with a poor prognosis. According to relevant studies, SAP30 may be associated with the growth, proliferation and apoptosis of renal cell carcinoma cells, and GO analysis of SAP30 downstream regulatory target genome showed that SAP30 repressed the expression of MT1G, a P53-binding protein. Mechanistically, SAP30 inhibits MT1G expression at the transcriptional level, reducing the ability of MT1G to deliver to zinc ions to P53, thus reducing P53 activity, and the downregulation of MT1G also attenuates the inhibition of MDM2, thereby reducing the stability of P53, which ultimately promotes the development of renal cell carcinoma. In summary, our study shows that SAP30 inhibits the P53 pathway by inhibiting MT1G, suggesting that SAP30 and MT1G may become markers of renal cell carcinoma prognosis and therapeutic targets.