表观遗传修饰与肿瘤的发生和发展密切相关，可作为早期诊断和预后的指标。肾细胞癌（RCC）的发生常伴随着表观遗传学的改变，但目前尚缺乏相关标志物。本课题组前期筛选出三结构域蛋白家族成员TRIM58，并发现：1）相比于正常细胞系和癌旁组织，TRIM58在肾癌细胞系和肾癌组织中表达明显下降；2）去甲基化药物处理后可恢复TRIM58的表达；3）肾癌组织的TRIM58甲基化水平显著高于癌旁组织。我们推测：TRIM58甲基化和羟甲基化在RCC的发生发展中起重要作用。本项目将在前期基础上，拟进行：1）研究TRIM58在RCC中的甲基化及羟甲基化水平；2）研究TRIM58的表观修饰对其表达的调控作用及机制；3）研究TRIM58在RCC中的功能作用。本课题有望明确TRIM58在RCC的表观修饰及其功能和机制，为早期诊断和靶向治疗提供理依据和新的靶点。

Epigenetic modification is closely related to the tumor’s initiation and progression, Which can be used as an early diagnosis and prognostic markers. The development of renal cell carcinoma (RCC) is often accompanied with epigenetic changes, however currently RCC is short of related markers. Our research team preliminarily screened TRIM58 and find that: 1) The expression of TRIM58 was significantly decreased in both cancer tissues and cancer cell lines compared to adjacent normal tissues and normal cell lines; 2) The expression of TRIM58 was restored after demethylation treatment; 3) The Status of TRIM58 methylation was significantly different between cancer tissues and adjacent normal tissues. We speculate that the methylation and Hydroxymethylation of TRIM58 play an important role in the development of RCC. The project will be carried out on the basis of the previous work: 1) to examine the methylation and Hydroxymethylation level of TRIM58 in RCC; 2) to study the epigenetic regulatory effect of TRIM58 on gene expression and its mechanism; 3) to identify the functional effect of TRIM58 on RCC. This project is expected to clarify the epigenetic modification of TRIM58 and its function as well as mechanism in RCC ,with an aim to provide the theory basis and new therapeutic targets for early diagnosis and targeted therapy.