结直肠炎癌转化的确切分子机制尚不清楚。现有证据表明上皮间充质转变及其介导的肿瘤干细胞特性与炎性肠癌(Colitis Associated Cancer, CAC)的发生密切相关。前期工作发现CAC中的Twist1高表达，且可以促进CAC中的结直肠癌干细胞的自我更新；进一步发现Twist1可以与Ku70和Sirt1发生相互作用，共同形成转录复合体促进结直肠癌干细胞的自我更新和CAC的发生。本项目拟通过生化和分子生物学方法进一步确认Twist1/Ku70/Sirt1转录复合体及其核心成分，以及其对下游基因的转录调控模式；并在此基础上通过细胞功能实验、动物移植瘤和诱癌模型以及临床病理分析验证该转录复合体及其对靶基因的转录调控与CAC干性及肿瘤发生的关系。本项目有助于阐释Twist1通过表观遗传学调控机制介导CAC干性及肿瘤发生的分子机制，为结直肠炎癌转化的早期诊治提供理论基础。

The exact molecular mechanism of transition from colitis to cancer remains unclear. Current evidence suggests that Epithelial Mesenchymal Transition (EMT) and its induction of cancer stemness are closely related to tumorgenesis of Colitis Associated Cancer (CAC). Previous work has found that Twist1 is highly expressed in CAC and can promote the self-renewal ability of colorectal cancer stem cells (CCSCs). Further fishing for the interaction protein of Twist-1, we found that Twist-1 can interact with Ku70 and Sirt-1, and form a transcriptional complex to promote the self-renewal of CCSCs and the tumorgenesis of CAC. This project intends to further confirm the Twist1/Ku70/Sirt1 transcriptional complex and its core components, as well as its transcriptional regulation modes for downstream target genes, through biochemical and chemical biological techniques. We also intend to verify the promotion of self-renewal and tumorigenesis of Twist1/Ku70/Sirt1 transcription complex via functional experiments at cellular level, tumor-bearing mice model. The relationship between Twist1, cancer stem characteristics and CAC was further analyzed and verified clinicopathologically. On this basis, small molecule drugs targeting the transcription complex were screened, and their inhibitory effects on colon cancer stemness and CAC were then evaluated. This project is helpful to elucidate the molecular mechanism of Twist1 in mediating colon cancer stem characteristcis and the tumorgenesis of CAC by epigenetic regulation mechanism, and to provide theoretical basis for searching for early diagnostic markers of transition from colitis to cancer and developing drugs to inhibit the transformation from inflammation to cancer.