我们最近发表在Gastroenterology上的研究显示JMJD2D可以通过激活Wnt/β-catenin信号通路促进结肠癌的发展。目前，JMJD2D在肝癌中的作用仍然不清楚。我们前期研究发现JMJD2D蛋白在肝癌组织中过表达；下调JMJD2D可以抑制肝癌细胞的增殖，促进细胞凋亡，诱导p53靶基因（p21,PUMA和NOXA）的表达，但不影响β-catenin的表达；p21和PUMA基因上p53结合位点是JMJD2D调控p21和PUMA基因转录表达所必须的。因此，我们提出不同于结肠癌中JMJD2D的作用机制：JMJD2D可能通过抑制p53信号通路来促进肝癌的发展。本项目拟就如下科学问题开展研究：一.研究JMJD2D在肝癌细胞增殖，凋亡，耐药性以及小鼠原位肝癌形成中的作用；二.探讨JMJD2D调控p53靶基因表达的分子机制；三.分析JMJD2D和p53靶基因的表达与肝癌临床特征的相关性。

Our study published at Gastroenterology suggests that JMJD2D plays an important role through activating Wnt/β-catenin pathway in colorectal cancer. The role of JMJD2D in HCC progression remain unclear. Our preliminary results showed thatJMJD2D was overexpressed in human HCC; Downreguration of JMJD2D inhibited HCC cell proliferation ，induced cell apoptosis and promoted the expression of p53 target gene(p21,pUMA and NOXA), but did not affect β-catenin expression；p53 binding site in p21 and PUMA gene was required for that downregulation of JMJD2D promoted promoter activity of p21 and PUMA in HCC cells .Accordingly, we propose that JMJD2D promotes HCC progression through inhibiting p53 signal pathway. In this study, we will test this possibility. Firstly, we will detect the role JMJD2D in HCC proliferation，apoptosis, drug resistance and liver tumor formation in mice. Secondly, we will examine the molecular mechanism which JMJD2D regulates p53 signal pathway. Thirdly, we will examine the the correlation between the expression of JMJD2D and p53 target gene in HCC specimens as well as HCC progression.