胰腺癌干细胞在胰腺癌的侵袭转移、复发和化疗耐药中起着决定性的作用，加强胰腺癌干细胞分子机制的研究是治愈胰腺癌的关键所在。本研究小组前期研究证实miR-137在胰腺癌干细胞中低表达，增强其表达后发现RPTPβ/ζ信号通路关键蛋白——PTN表达被抑制，PTN在细胞侵袭转移、化疗耐药等方面具有重要意义，是RPTPβ/ζ信号通路关键效应因子。因此，提出miR-137调控PTN引起RPTPβ/ζ-β-catenin信号通路失调参与腺癌干细胞恶性生物学行为这一假说。本研究拟以临床原发胰腺癌组织标本、胰腺癌干细胞为研究对象，采用荧光素酶报告基因、免疫共沉淀及双分子荧光互补系统等分子生物学手段，确立miR-137与PTN的调控关系，阐明miR-137/PTN-RPTPβ/ζ-β-catenin信号通路各基因的关系及它们对胰腺癌干细胞恶性行为的影响，进一步阐明胰腺癌干细胞恶性生物行为的分子生物学机制。

Pancreatic cancer stem cells play a decisive role in the invasion and metastasis,recurrence and chemotherapy resistance in of pancreatic cancer, so the study of the molecular mechanisms is the critical. Our study group pre-test confirmed mircroRNA-137 low expression in pancreatic cancer stem cells, after enhanced miRNA-137 expression, the PTN-RPTPβ/ζ signaling pathway key protein-pleiotrophin (PTN) expression was suppressed，suggesting that miR-137 may cause PTN-RPTPβ/ζ-β-catenin signaling pathway abnormalities and involve in the malignant behavior of cancer stem cells by regulation PTN.Therefore, we propose a hypothesis that miR-137 regulation PTN caused RPTPβ/ζ-β-catenin signaling pathway disorders involved in the malignant behavior adenocarcinoma of stem cells. To test this hypothesis, our project will use primary pancreatic tissue and pancreatic cells, pancreatic stem cells，and dual luciferase reporter system, CoIP and BiFC to clarify miR-137/PTN-RPTPβ/ζ-β-catenin the relationship of each gene, and its effect on the malignant behavior of pancreatic cancer stem cells. This project is expected to further elucidate the molecular biological mechanisms of cancer stem cell malignant biological behavior.