肝癌是最常见的，多基因参与的恶性肿瘤之一。HOXD3基因在肺癌、乳腺癌等癌症中表达上调。而miR-203a在胶质母细胞瘤和肝癌等中表达下调，发挥着抑癌基因的作用。我们前期工作发现HOXD3在肝癌组织中高表达，与miR-203a的表达呈负相关。生物信息学预测可知HOXD3和miR-203a存在靶向关系。推测HOXD3可以被miR-203a靶向结合，参与肝癌的发生机制。本研究拟通过 HOXD3和miR-203a在肝癌组织及细胞系中的表达，分析其与临床病理指标的相关性；利用细胞生物学实验研究miR-203a对肝癌细胞生物学行为的影响；通过双荧光报告载体检测HOXD3与miR-203a的靶向性；采用RNA干扰和过表达HOXD3来抑制和恢复HOXD3的表达，研究HOXD3对下游细胞信号通路的调控作用；通过裸鼠成瘤实验验证HOXD3在体内对肝癌发生的作用机制，为探讨新的肝癌治疗手段奠定理论基础。

Human hepatocellular carcinoma is one of the most prevalent cancer, and many genes are involved in. The over-expression of HOXD3 gene is found in lung cancer, breast cancer and so on. However, miR-203a plays the role of tumor suppressor gene and its expression is down-regulated in gioblastoma cells and HCCs.Previously, we found that HOXD3 was up-regulated in tissues of HCC, and had negative correlation with miR-203a.So we hypothesize that HOXD3 is important in hepatocarcinogenesis by the regulation of miR-203a. First, we examine the expression of HOXD3 and miR-203a in hepatocellular cacinoma tissues and cells to find the relationship between their expression and clinicopathological parameters. Second, we investigate the effects of miR-203a on function of HCCs and confirm the relationship between HOXD3 and miR-203a by dual luciferase reporter system. Third, through the transfection of siHOXD3 or HOXD3 vector, we verify the role of HOXD3 on its related signal pathways. Finally, we investigate the HOXD3 influence on tumor formation in vivo through a xenograft model to offer potential targets for therapy of HCC.