参与乳腺肿瘤转移的miRNA筛选及机制研究

项目名称： 参与乳腺肿瘤转移的miRNA筛选及机制研究

项目编号： No.81472660

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： 李义

作者单位： 中国医学科学院肿瘤医院

项目金额： 64万元

中文摘要： 侵袭转移是恶性肿瘤致死的主要原因，上皮-间质转化(EMT)则在肿瘤侵袭转移过程中发挥关键作用。EMT受多因素调控，包括细胞因子、转录因子和miRNA等。目前对miRNA参与侵袭转移调控研究刚刚起步。本课题以乳腺癌为研究对象，通过在低转移乳腺癌细胞系中建立稳定表达miRNA文库再经过体内小鼠转移模型和体外侵袭模型来筛选促进侵袭转移和EMT过程的miRNA。并结合TGF-β和Snail诱导EMT细胞模型的表达谱进行分析来确立参与乳腺肿瘤侵袭转移调节的miRNA。初期筛选研究显示miR-578j、miR-182、200c等多种miRNA参与乳腺肿瘤侵袭转移过程的调节。因此需要进一步在细胞水平、动物水平上研究这些miRNA在肿瘤侵袭转移过程中的功能；同时寻找其靶基因来探索它们发挥作用的分子机制。最后通过在临床组织标本中表达分析来阐明其在临床应用中的意义，为将来能成为临床诊断分子标志提供理论基础。

中文关键词： C21_乳腺肿瘤；上皮-间质转化；肿瘤转移；微RNA

英文摘要： Tumor metastasis is primarily responsible for cancer-associated mortality. Epithelial mesenchymal transition (EMT) is a cell reprogramming process, and plays an important role in tumor invasion and metastasis. EMT is regulated by many factors, including the cytokines, transcription factors and miRNAs. So far, the role of miRNA in EMT is still poorly understood. In this project we attempt to identify metastasis associated genes and miRNAs, we designed a serial of screening models, such as in vivo mouse screening model and in vitro transwell screening model, to screen miRNAs involved in EMT and metastasis in SKBR3 and MCF7 cell pools expressing miRNAs libraries, as well as analysis of gene expression profiling of TGF-β and Snail induced EMT model in MCF10A. In addition, we clarify the mechanisms of how miRNAs regulate metastasis. Our preliminary data showed that miR-578j, miR-182, miR-200c, and other miRNAs involved in regulating tumor invasion and metastasis process. Therefore, we need to further clarify the function of these miRNAs at the cellular and animal level, and also to explore its molecular mechanism in the process of invasion and metastasis through indentifying the targets of miRNAs. Moreover, miRNAs signatures identified in this project can delineate their clinical significance for breast cancer, and may provide new molecular approaches for diagnosis and prognosis of patients.

英文关键词： Breast Cancer;EMT;Tumor metastasis;microRNA