健脾复方通过MALAT1调节PTBP-2激活β-catenin信号通路抑制大肠癌侵袭转移的机制

项目名称： 健脾复方通过MALAT1调节PTBP-2激活β-catenin信号通路抑制大肠癌侵袭转移的机制

项目编号： No.81473628

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： 任建琳

作者单位： 上海中医药大学

项目金额： 72万元

中文摘要： 侵袭转移是大肠癌治疗失败的主要原因之一，近年来研究发现长链非编码RNA-MALAT1参与了大肠癌的侵袭转移，但确切机制尚不清楚。我们前期研究发现MALAT1促进β-catenin的核转运引起癌细胞的侵袭迁移，并能解离SFPQ/PTBP-2复合物，释放PTBP-2；健脾复方能够抑制大肠癌侵袭转移，抑制MALAT1。因此我们提出MALAT1可能通过PTBP-2激活β-catenin信号通路是大肠癌侵袭转移的重要机制之一。本课题构建MALAT1慢病毒载体，采用质粒转染等技术，从MALAT1调节PTBP-2激活β-catenin信号通路的介导来揭示大肠癌侵袭转移的机制；并建立裸鼠肠癌转移模型，通过体内和体外研究健脾复方调控MALAT1/PTBP-2/β-catenin信号传递，抑制大肠癌侵袭转移的作用机理，为中医药防治大肠癌复发转移提供研究思路和实验基础。

中文关键词： 大肠癌；MALAT1；β-catenin信号通路；侵袭转移；健脾复方

英文摘要： Metastasis is one of the main reasons why therapies fail in treating colon cancer (CC). The non-coding long RNA MALAT1 has recently found to regulate cell invasion and metastasis, but the mechanism remains elusive. We previously reported that MALAT1 enhances nuclear translocation of beta-catenin resulting in increased cancer cell metastasis, while dissociating heterodimer SFPQ/PTBP-2 to release PTBP-2. We also showed that TCM Jianpifufang (JPFF) inhibits MALAT1 expression as well as decreases CC metastasis. Here we postulate the MALAT-1-PTBP-2-beta-catenin signaling axis as one of the main mechanisms regulating cancer metastasis. We propose to generate MALAT1 lentiviral vector, use plasmid transfection and CC cell lines HT-29, SW48, to delineate this aforementioned signaling cascade. We will further substantiate the inhibitory effect of JPFF on MALAT1 expression and PTBP-2 dependent beta-catenin activation, consequently decreasing cancer metastasis. This study of ours will shed light on the mechanisms by which CC cells metastasize, and equally importantly, identify novel oncogenic therapeutic targets for using TCM to prevent and cure cancers.

英文关键词： Colorectal cancer;Metastasis Associated in Lung Adenocarcinoma Transcript 1;β-catenin signal transduction;Invasion and Metastasis;Jianpi Compound Recipe