职业性镉暴露导致的肾损伤缺乏有效的诊疗手段，防治的关键在于阐明毒性机制并寻找早期生物学标志。前期研究在镉暴露后随访人群中发现miRNA-363-3p高表达，而且与肾小管损伤标志物尿β2-MG有相关性。生物信息学分析提示，ABC转运体是miRNA-363-3p的潜在靶基因，ABCB5和ABCC11通过膜转运通路间接影响细胞周期相关蛋白TP53。因此，我们首次提出miRNA-363-3p可能靶向结合ABC转运体介导镉暴露致肾小管早期损伤。本项目拟利用前期筛选的miRNA-363-3p在职业人群中评估其作为肾小管损伤早期监测生物标志物的可行性；体外实验应用报告基因系统、RNA免疫沉淀等技术，结合镉致肾小管早期损伤动物模型，通过基因功能获得和功能缺失策略，研究miRNA-363-3p对ABC转运体的转录后调控及其在肾损伤发生发展过程中的作用通路，为职业性镉暴露肾损伤干预靶点提供新策略。

Cadmium nephrotoxicity caused by occupational exposure lacks effective diagnosis and treatment. The key to prevention is to elucidate the molecular mechanisms and identify the specific biomarkers. In our previous studies, we found the high expressions of miRNA-363-3p were related withβ2-microglobulin ,characterized by renal tubular injury marker in urine of the follow-up workers after cadmium exposure. Bioinformatics analysis suggested that ABC transporter was a potential target gene of miRNA-363-3p, ABCB5 and ABCC11 indirectly affected cell cycle-related protein TP53 through the membrane transport pathway. For the first time, we propose that miRNA-363-3p may targets the ABC transporters in pathological process of nephrotoxicity caused by cadmium occupational exposure. In this project, we will further investigate whether miRNA-363-3p as a specific biomarker to evaluate the early renal tubular injury in the occupational workers. Moreover, we will identify effects of ABC transporters posttranslational regulated by miRNA-363-3p in vitro cell model by luciferase reporter system and RNA binding protein immunoprecipitation technology. Furthermore, we will explore the function and molecular mechanism of targeting ABC transporters modification of miRNA-363-3p in the occurrence and development of nephrotoxicity by gain-of-function, loss-of-function strategy in knockout mice. This project will provide a novel strategy for targeted intervention of cadmium nephrotoxicity in occupational population.