SARI基因是一个重要的转录因子和抑癌基因，我们发现SARI是一个新的肿瘤血管生成抑制因子（Dai L, et al. Nature Communications. 2016），在人结肠癌中低表达。进一步研究发现SARI在AOM+DSS诱导的结肠“炎-癌”过程中表达下调，也在多种结肠癌细胞中存在DNA甲基化介导的表达失活，但机制不清楚，也未见文献报道。为了阐明SARI基因在结肠癌中表达失活机制及特异性去除SARI甲基化后的功能，本课题将利用亚硫酸盐处理-甲基化特异性PCR-TA克隆检测80-100例不同临床分期的人结肠癌组织中SARI基因的甲基化位点、分布情况以及与患者临床分期和预后的相关性；利用dCas9技术特异性解除结肠癌细胞中SARI基因的甲基化，研究特异性去除SARI甲基化后对结肠癌生长的调控作用，为阐明SARI基因在结肠癌中的失活机制奠定基础，也为未来结肠癌的治疗提供潜在的靶点。

SARI gene is an important transcription factor and tumor suppressor gene. We found that SARI is a novel suppressor of tumor angiogenesis (Dai L, et al. Nature Communications. 2016), and low expression in human colon cancer. Further studies have demonstrated that SARI was down-regulated during AOM+DSS-induced colitis associated colon cancer. And DNA methylation-mediated SARI inactivation was found in various colon cancer cells. But, until now, the mechanism was still unclear and without literature reporting. In order to elucidate the mechanism of SARI gene inactivation in colon cancer and the effects of SARI demethylation specifically, sulfite treatment - methylation specific PCR-TA cloning are performed to detect the methylation site of SARI in 80-100 colon cancer tissues of patients with different clinical staging. The correlation between SARI methylation and the clinical staging and prognosis of patients were analyzed. Furthermore, dCas9-based demethylation technique was employed to remove the methylation of SARI gene in colon cancer cells specifically and investigate the effect of SARI demethylation on colon cancer growth. The present study would lay the foundation for understanding the mechanism of SARI inactivation in colon cancer and provide a potential therapy target for colon cancer.