有机阳离子转运体OCT2由SLC22A2基因编码，在肾组织中高表达，转运铂类抗癌药物进入肾细胞，而肾癌对化疗广泛耐药。我们的研究表明，在肾癌组织中SLC22A2低表达，其DNA甲基化发挥了重要作用（Sci Transl Med,2016）。在此基础上，本项目进一步揭示SLC22A2组蛋白乙酰化修饰H3K18Ac/K27Ac和miR-630/miR-489-3p参与肾癌SLC22A2基因转录调节的机理，探究肾癌中SLC22A2组蛋白乙酰化或miRNA与DNA甲基化之间的关系；并基于肾癌中SLC22A2的表观遗传学机理，从RCC细胞、RCC细胞异种移植瘤裸鼠和PDX模型的体内外实验，设计表观遗传药物与OCT2底物奥沙利铂治疗RCC的联合给药方案，并验证其有效性和安全性。本研究将丰富RCC中SLC22A2基因调节信号通路,完善SLC22A2基因表观遗传调控机理，为临床诊断和治疗RCC提供依据。

Organic cation transporter OCT2 encoded by the SLC22A2 gene is highly expressed in renal tissue and translocates platinum-like anticancer drugs into renal cells. Kidney cancer is highly resistant to chemotherapy. Our previous studies have shown that SLC22A2 is low in renal cell carcinoma and its DNA methylation plays an important role（Sci Transl Med,2016）. On the basis of this, this project further revealed tht histone acetylation H3K18Ac/K27Ac and miR-630/miR-489-3p involved in the regulation of SLC22A2 gene transcriptional regulation in renal cell carcinoma, and the relationship between histone acetylation or miRNA and DNA methylation of SLC22A2 in renal cell carcinoma. The combined administration of epigenetic drugs with OCT2 substrate oxaliplatin in the treatment of RCC in vitro and in vivo is designed using RCC cells, RCC cell xenograft nude mice and PDX models and the pharmacological mechanism and toxicity are studied. This study will enrich the SLC22A2 regulatory pathway in RCC, improve the epigenetic regulation mechanism of SLC22A2, and provide theoretical and experimental basis for clinical diagnosis and treatment of RCC.