G9a是近年研究活跃的一个组蛋白甲基转移酶，主要催化H3K9甲基化维持基因沉默及DNA甲基化。已有研究证实G9a在多种肿瘤中过表达，敲除G9a可抑制细胞增殖，但机制不明，且未见其在结直肠癌（Colorectal Cancer，CRC）中的相关报道。我们首次证实G9a在CRC病人的肿瘤组织中显著高表达，且高表达G9a明显促进CRC体内外生长，而干扰G9a或使用抑制剂则显著抑制生长，提示G9a有望成为CRC治疗的新手段。深入研究发现G9a可能通过调控Polo-like kinase（Plk），这一参与有丝分裂调节、促进增殖的丝/苏氨酸蛋白激酶影响CRC发展。本课题以Plk为切入点，希望阐明G9a调控Plk进而影响CRC发生发展的具体分子机制，从而丰富对G9a功能和机制的认识，也进一步确定G9a是否可成为CRC治疗的新靶点，为这一发病率世界第三、死亡率第四的恶性肿瘤寻求新的治疗可能。

Recently, histone methytransferase G9a has become another hot area of epigenetics research. It always catalyzes mono- and di-methylation of histone H3 Lys9 (H3K9me1/H3K9me2). Growing evidence suggests that G9a is required for the maintenance of the malignant phenotype. However, the tumorigenic role of G9a in colorectal cancer (CRC) is far from clear. Recently, we identified for the first time that G9a was highly expressed in colorectal cancer tumor tissues, and over-expression of G9a stimulated CRC cells proliferation both in vitro and in vivo. Moreover, G9a knockdown, and G9a specific inhibitors inhibit CRC cells proliferation. Therefore, in this study, we would like to explore the exactly mechanisms of G9a on promoting CRC progress. We already found that the polo-like kinase (Plk1), a crucial driver of CRC proliferation, can be downregulated by knockdown of G9a. In this study, we want to know how G9a leads to increased expression of Plk1 and promote CRC proliferation. All the results obtained in this study will strengthen our current knowledge of G9a, and indicate that G9a inhibition may be a promising therapeutic target in the treatment of CRC.