上皮间质转化（EMT）是促进胰腺癌干性转化和侵袭转移的重要因素。课题组前期研究发现上调miR-148a可抑制胰腺癌生长，但机制尚不明确。Wnt1/10b可以激活Wnt/β-catenin信号通路而诱导EMT。我们预实验证实胰腺癌中miR-148a可靶向调控Wnt1/10b；抑制DNMT1活性可使miR-148a基因启动子去甲基化而上调其表达水平。故推测胰腺癌中存在DNMT1-miR-148a-Wnt1/10b调控轴持续下调miR-148a、上调Wnt1/10b的表达，激活Wnt/β-catenin信号通路介导EMT，促进干性转化和侵袭转移。本课题首先分析该调控轴中各分子在胰腺癌组织中表达的相关性，然后经体外实验干预调控轴中各分子的表达，明确其上下游调控关系及诱导EMT和干性表型的作用机制，最后经裸鼠移植瘤实验进一步体内验证。研究结果有望为抑制胰腺癌EMT和干性转化的靶向治疗提供新的切入点。

Epithelial mesenchymal transition (EMT) is an important promoting factor on the stemness transformation and metastases of pancreatic cancer. Our previous studies indicated that up-regulation of miR-148a could inhibit the growth of pancreatic cancer, while its mechanism is still unkown. Wnt1 and Wnt10b can promote EMT process through activing Wnt/β-catenin signaling pathway. We found that Wnt1/10b were two direct targets of miR-148a by miRNA targets prediction softwares, luciferase reporter assay and pancreatic cancer cell in vitro study. The inhibition of DNMT1 activity could up-regulation the expression of miR-148a through demethylation of its gene promoter. Therefore, we deduce there may be an DNMT1-miR-148a-Wnt1/10b regulating axis to continuously downregulate miR-148a expression, upregulate Wnt1/10b expression, activate Wnt/β-catenin signaling pathyway which eventually result in the induction of EMT, promote stemness transformation and metastases in pancreatic cancer. To clarify this deduction, we plan to analysis the expression status and their relationship of each molecule of DNMT1-miR-148a-Wnt1/10b regulating axis in pancreatic cancer specimens. The regulatory relationships and the effects on induction of EMT and stemness phenotype in pancreatic cancer of DNMT1-miR-148a-Wnt1/10b regulating axis will also be determined in vitro and in vivo experiments. The study will provide new target for the treatment of pancreatic cancer by inhibition of EMT and stemness transformation.