Wnt/β-catenin（Wnt）通路是调控细胞干性的重要信号通路。非编码RNA作为Wnt通路的重要效应因子，参与Wnt驱动的基因表达程序。但Wnt通路能够直接控制多少lncRNA的表达及其在结肠癌干细胞中的作用仍有待阐明。我们前期通过抑制结肠癌干细胞的Wnt通路，发现一批lncRNA的表达发生显著变化，其中WTL的转录调控区存在TCF/LEF1结合位点，并在结肠癌中显著上调，且与OCT4等干细胞核心基因群共表达。本项目以此为突破口，整合结肠癌干细胞中转录组和表观组高通量测序数据，系统地鉴定与研究结肠癌细胞Wnt通路相关的lncRNA及其转录调控，解析WTL及其结合蛋白的功能机制以及对结肠癌细胞干性维持与耐药的影响。这项研究将深入揭示Wnt通路介导的lncRNA信号传导及调控网络，对阐明Wnt在结肠癌干细胞中的作用机制、并提供新的结肠癌治疗策略具有重要意义。

Wnt/β-catenin pathway (Wnt pathway) has pivotal roles in the regulation of cell stemness. Recently, non-coding RNAs have been found to be important Wnt pathway effectors and to participate in WNT-driven gene expression programs. However, the number and functions of Wnt pathway regulated lncRNAs in colon cancer stem cells (CCSCs) remain to be elucidated. In our previous studies, the transcriptome analyses in CCSCs showed that a batch of lncRNAs were significantly altered upon inhibition of Wnt pathway activity. And a lncRNA named WTL has TCF/LEF1 binding sites within its transcription regulatory region. Moreover, WTL is upregulated in Colon Cancer and co-expressed with the core genes of stem cells including OCT4. Based on the above findings, the project will systematically identify the Wnt pathway regulated lncRNAs and analysis their transcriptional regulation based on integration of transcriptome and epitranscriptome high-throughput sequencing datasets. Furthermore, we will demonstrate the molecular mechanisms of WTL and its RNA binding proteins as well as their functions involved in Colon Cancer cells maintenance and treatment resistance. Thus the study will reveal Wnt pathway-mediated lncRNA signal transduction and regulatory network, illustrate the functions of Wnt signaling pathway in CCSCs and provide new targets for treatment of Colon Cancer.