miR-363调控肺腺癌干细胞促进肿瘤转移的分子机制研究

项目名称： miR-363调控肺腺癌干细胞促进肿瘤转移的分子机制研究

项目编号： No.81472174

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： 卢韶华

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 肿瘤转移是影响肺癌预后的关键因素。在肺癌侵袭转移链中，EMT (epithelial mesenchymal transition)是肺癌转移的重要驱动力，而CSC(cancer stem cell)是肺癌转移的决定性因素。前期工作我们通过激光捕获显微切割从转移组及非转移组肺腺癌组织中分离纯净肿瘤细胞，进行Aglient miRNA芯片分析,筛选出表达显著升高且居首的miR-363，且证实miR-363在肺腺癌EMT、侵袭及转移中起着关键作用。本项目拟以肺腺癌干细胞及临床肺腺癌标本为研究对象，进一步观察miR-363对Numb、E-cadherin和β-catenin分子表达、亚细胞定位、代谢及转录功能变化，探讨miR-363对Wnt/β-catenin及Notch信号通路传导的影响及其在肺腺癌干细胞促进肿瘤转移中的作用，为基于miR-363的肺腺癌转移分子预测及靶向治疗奠定理论基础。

中文关键词： C05_气管；支气管；肺肿瘤；miR-363；肿瘤干细胞；转移；信号通路

英文摘要： Tumor metastasis is a pivotal factor on lung adenocarcinoma(AC) prognosis. Epithelial and mesenchymal transition(EMT) has been thought to be an important driver of cell invasive of AC, while cancer stem cell(CSC) has been thought to be a determined factor of AC colonization and outgrowth in a distant organ. In our previous study, we have screened out miR-363，the top miRNA marker which is highly expressed in metastatic AC by laser capture microdissection（LCM）and Agilent miRNA assay. We also confirmed that miR-363 was able ro negatively regulate the EMT, proliferation and local invasion of AC. In this project, wo want to continuously explore the effects of miR-363 on expressions, subcellular localization, recyclings and transcriptional activities of Numb, E-cadherin and beta-catenin using AC stem cells, as well as surgical tissues from clinic. Furthermore, we want to elucidate the regulatory roles of miR-363 in tumor metastasis of AC via Wnt/beta-catenin and Notch signaling pathways, for establishing a theoretical basis of AC prognosis and therapeutics based on miR-363.

英文关键词： C05-barochial and lung cancer;miR-363;cancer stem cell;metastasis;signaling pathways