大肠癌的发生涉及遗传与表观遗传的异常。Ets转录因子家族在肿瘤的发生发展中发挥重要作用，Elf3是一个上皮特异性Ets转录因子，其在大肠癌中的作用尚不明确。我们研究表明，Elf3在大肠癌中发挥癌基因功能，且其功能与激活β-catenin表达有关，但机制尚不明确。天然反义转录本（NAT）作为一种重要的表观遗传调控方式越来越受到重视。前期研究发现，Elf3天然反义转录本（Elf3-NAT）可以抑制Elf3的表达，但具体机制仍不明确。本课题将在前期研究基础上，进一步明确以下问题：（1）Elf3能否结合到β-catenin的启动子并直接激活其转录及对其胞浆胞核分布的影响。（2）Elf3-NAT是否通过双链依赖机制抑制Elf3表达，是否依赖Dicer/Drosha酶？（3）Elf3-NAT在大肠癌中是否发挥抑癌基因功能？本课题首次探讨NAT在大肠癌发生中的作用，将为大肠癌发生的分子机制提供重要补充。

Both genetic and epigenetic abnormalities contribute to the colorectal tumorigenesis.Ets transcription factors play important roles in tumorigenesis .Elf3 is an epithelial -specific Ets transcription factor ,and its role in colorectal cancer(CRC) is not yet clear. Our previousstudy have shown that Elf3 functions as an oncogene in CRC by activating β-catenin, but the detailed mechanism has not been elucidated.There has been increasing attention to the significance and roles of natural antisense transcript (NAT) in terms of epigenetic regulation.Our preliminary study have shown that the NAT of Elf3 (Elf3-NAT) could repress the expression of Elf3, but the detailed mechanism remained unclear. This study is going to further clarify the following questions based our preliminary studies: (1)Does Elf3 bind to the promoter of β-catenin , activate its transcription directly, and influence the distribution of β-catenin? (2)Does Elf3-NAT repress the expression of Elf3 in a dsRNA-strand mechanism and in a Dicer/Drosha dependent manner? (3)Does Elf3-NAT function as a tumor suppressor gene in CRC? This is the first study to investigate the role of NAT in colorectal carcinogenesis, and is opt to provide an important complement for the molecular mechanism of CRC.