肝癌的发病机制尚未阐明，探索新的基因功能改变与调控机制，将有助于揭示肝癌发生发展的分子机制。锌α2糖蛋白(ZAG)异常表达与肿瘤的发生发展密切相关，但其在肝癌中的表达调控机制缺乏深入的研究。我们前期发现核糖核苷酸还原酶M2B(RRM2B)能抑制肝癌转移，RRM2B能够上调ZAG 的表达，提示在肝癌中RRM2B可能参与对ZAG的表达调控；ZAG在肝癌组织中表达降低，并能抑制细胞增殖、侵袭和迁移，提示ZAG与肝癌的发生发展密切相关，但其具体分子机制不清。本研究拟通过大规模肝癌临床样本和DEN诱导的肝癌小鼠模型研究ZAG和RRM2B在肝癌不同发展时期的作用；采用报告基因、ChIP等检测技术阐明ZAG在肝癌中表达调控机制；利用基因芯片、定量PCR、transwell及动物实验等技术探讨ZAG在肝癌中的功能及作用机制。通过阐明ZAG在肝癌中的表达调控机制，为探索肝癌的发生机制及治疗策略提供新的思路。

The pathogenesis of the hepatocellular carcinoma (HCC) has not been elucidated. The discovery of function and regulatory mechanism of new gene will be useful to reveal the molecular mechanism of HCC development and progression. Zinc-alpha2-glycoprotein （ZAG）is closely related with development and progression of tumors. But the expression and regulatory mechanisms of ZAG in HCC remain unclear. Our previous study showed that ribonucleotide reductase M2B (RRM2B) inhibited metastasis of HCC. RRM2B increased expression of ZAG in HCC cells. It means that RRM2B may be involved in the regulation of ZAG gene expression in HCC. The expression of ZAG was down-regulated in HCC tissues compared with non-cancerous liver tissues. In addition, overexpression of ZAG inhibited the proliferation，migration and invasion of HCC cells in vitro. These results suggest that ZAG may be closely related with development and progression of HCC. On base of these results, we will try to clarify the role of ZAG and RRM2B in hepatocellular carcinoma and DEN induced liver cancer mouse model. We will try to explore the molecular mechanisms of ZAG expression using luciferase assay and ChIP assay.We will clarify the function of ZAG in HCC and its molecular mechanisms using cDNA microarray, realtime RT-PCR, transwell assay and animal experiment. The results not only illustrate the regulatory mechanism of ZAG expression in development and progression of HCC, but also provide new ideas on the pathogenesis and therapeutic targets of HCC.