PARP1、miR-223和H-RAS是肿瘤临床治疗的核心靶点，在细胞分化、增殖和凋亡等过程中起重要作用，已证实其异常表达与肿瘤有关。本项目拟在前期研究基础上以苯代谢物氢醌诱发恶变细胞为模型，动态分析PARP1、miR-223和H-RAS表达，初步建立PARP1与miR-223负反馈调控环及其介导的miR-223/PARP1/H-RAS通路。在细胞内，以RNA干扰、PARP抑制剂与诱导剂、ChIP和报告基因研究PARP1调节miR-223和H-RAS的机制，以miR-223表达载体和报告基因研究阐明miR-223调节PARP1机制；在细胞和动物体内，揭示miR-223/PARP1/H-RAS通路异常的生物学功能。本项目将首次揭示PARP1与miR-223负反馈调控环介导的miR-223/PARP1/H-RAS通路异常在氢醌诱癌过程中的作用及分子机制，为阐明环境致癌机制及其防治提供新思路。

PARP1, miR-223 and H-RAS, critical therapeutic targets in tumor clinical treatment, play important roles in cell differentiation, proliferation and apoptosis, and are verified to be associated with tumor. Based on previous study, this project will test the expressions of PARP1, miR-223 and H-RAS dynamicly in hydroquinone induced malignant transformation cells, to establish miR-223/PARP1/H-RAS pathway which mediated by a negative regulatory loop composed by PARP1 and miR-223. Using RNA interference, PARP inhibitors and inducer, ChIP and luciferase report assay to identify the mechanism of miR-223 and H-RAS mediated by PARP1 in vitro, in the versus, illustrate the mechanism of PARP1 mediated by miR-223 through miR-223 expression vector and luciferase report assay. Uncover the biological functions of aberrant miR-223/PARP1/H-RAS pathway both in vivo and in vitro. It would be the first time to demonstrate the function and molecular mechanism of aberrant miR-223/PARP1/H-RAS pathway mediated by the negative feedback composed by miR-223 and PARP1 in the hydroquinone induced tumor formation course，making new direction for the mechanism of environmental carcinogenesis.