Guo Wei, Wang Shuwen, Yang Zitong, Dong Yu, Xia Zhinan, Xue Wei, Zhang Cheng
Department of Urology, Center for Oncology Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Eur J Med Res. 2025 Apr 18;30(1):306. doi: 10.1186/s40001-025-02440-7.
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.
Sin3A相关蛋白30（SAP30）是SIN/HDAC组蛋白去乙酰化酶复合体的关键组成部分，作为一种支架促进靶基因结合。SAP30在多种肿瘤中高表达；然而，其在肾细胞癌（RCC）中的作用仍不清楚。在我们的研究中，我们观察到透明细胞肾细胞癌（ccRCC）组织中SAP30上调，其表达升高与预后不良相关。先前的研究表明，SAP30可能影响RCC细胞的生长、增殖和凋亡。对SAP30下游调控靶点的基因本体论（GO）分析显示，SAP30抑制与p53结合的蛋白MT1G的表达。机制上，SAP30抑制MT1G转录，从而损害MT1G将锌离子传递给p53的功能，降低p53活性。此外，MT1G水平降低减弱了MT1G对MDM2的抑制作用，进一步使p53不稳定。因此，这一信号级联促进了RCC进展。总之，我们的研究结果表明，SAP30通过抑制MT1G抑制p53通路，提示SAP30和MT1G是RCC潜在的预后标志物和治疗靶点。
