miR-195靶向LRP6调控Wnt/β-catenin信号通路抑制大肠癌侵袭转移及健脾解毒方对其作用的研究

项目名称： miR-195靶向LRP6调控Wnt/β-catenin信号通路抑制大肠癌侵袭转移及健脾解毒方对其作用的研究

项目编号： No.81473478

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李琦

作者单位： 上海中医药大学

项目金额： 73万元

中文摘要： 侵袭转移是影响大肠癌预后的重要因素，Wnt/β-catenin信号通路在大肠癌侵袭转移中起重要作用，成为肿瘤治疗的重要靶点。但Wnt/β-catenin信号通路的调控机尚不清楚，为临床防治带难题。 前期研究发现细胞膜上的Wnt信号通路的受体LRP6和miR-195表达呈负相关，健脾解毒方能抑制大肠癌侵袭转移，上调miR-195，抑制β-catenin信号通路。我们推测miR-195可能靶向LRP6调节Wnt/β-catenin信号通路是大肠癌侵袭转移的重要途径之一。因此，本研究构建LRP6 3'UTR报告基因、miR-195慢病毒载体，研究miR-195靶向LRP6调控β-catenin信号通路抑制大肠癌侵袭转移的机制，并深入探讨健脾解毒方对miR195- - LRP6- - β-catenin生物信息传递的调节机制。这对于揭示大肠癌侵袭转移的机制，明确中药防治大肠癌的靶点具有重要的科学意义。

中文关键词： 大肠癌；侵袭转移；microRNA；Wnt/β-catenin；健脾解毒方

英文摘要： The prognosis of colon cancer (CC) is critically affected by tumor cell invasion and metastasis, a process in which wnt/beta-catenin signaling pathway plays a major role, and is often targeted by therapies. But how beta-catenin signaling is regulated remains unclear, thus makes it hard to develop any meaningful therapeutic approach. Our preliminary data uncovered a negative correlation between the expression levels of upstream receptor LRP6 and miR-195; Jianpi Jiedu Recipe upregulated miR-195 expression, repressed beta-catenin signaling, consequently inhibited CC cell invasion and metastasis. We hypothesize that a miR-195-LRP6-wnt/beta-catenin signaling axis may mediate CC metastasis. We propose to use LRP6 3 'UTR reporter construct, miR-195 lentiviral vector, to study the underlying mechanism of this signaling cascade, and elucidate how Jianpi Jiedu Recipe affects it. This study of ours will shed light on the mechanisms by which CC cells metastasize and identify novel therapeutical targets for TCM.

英文关键词： Colorectal cancer;Invasion and Metastasis;microRNA;Wnt/β-catenin;Jianpi Jiedu Recipe