选择性剪接因子的异常表达是肿瘤发生发展的重要因素。多聚嘧啶结合蛋白1（PTBP1）作为一种剪接调控因子，在多种恶性肿瘤高表达，并与淋巴结转移相关，提示是一个潜在治疗靶点。然而，关于PTBP1为何高表达及在结直肠癌的作用和机制尚不明确。本项目前期发现PTBP1在结直肠癌高表达，促进肿瘤发生、侵袭和EMT，并激活Wnt/β-catenin信号通路；针对其上游，发现PTBP1受到miR-133b直接转录调控。本项目拟通过细胞学和分子生物学实验进一步从体内和体外评价PTBP1在结直肠癌的功能和临床意义；评估PTBP1在rTGF-β1介导的EMT中的作用；并揭示GSK-3β在PTBP1激活Wnt/β-catenin通路中的关键作用，以及敲低PTBP1对miR-133b诱导的EMT的阻断作用。完成该项目后，将揭示结直肠癌发生和转移的新的分子机制，提供肿瘤不良预后新指标，并为其早发现和早治疗提供新思路。

Ectopic expression of alternative splicing factors plays an important role in malignant tumors. Polypyrimidine tract-binding protein 1 (PTBT1) is over-expressed in various kinds of malignant tumors and has a positive relation with poor survival and lymph node metastasis, which indicate that PBPT1 might be a potential therapy target. However, the reason of PTBP1-overexpression and its mechanism is not clear. In our preliminary experiments, we found that PTBP1 is overexpressed in colorectal cancer and plays an important role in tumor development, invasion and epithelial-mesenchymal transition (EMT). PTBP1 can active the transcriptional activity of Wnt/β-catenin signal pathway. We also found that PTBP1 is regulated by miR-133b. In this study, a series of cell biological and molecular biological techniques and methods will be applied to detect the role and clinical significance of PTBP1 in colorectal cancer in vitro and in vivo, to detect the role of PBPT1 in rTGF-β1-induced EMT, the involvement of GSK-3β in PTBP1-induced Wnt/β-catenin pathway activity and the blockage of PTBP1 inhibition in miR-133b-induced EMT. After that, a new molecular mechanism of colorectal cancers tumorigenesis and metastasis and a potential prognostic marker will be revealed, which will provide new ideas for the early diagnosis and treatment of colorectal cancers.