ZEB1-miR-300-FAK通路在肝癌上皮-间质转化中的作用及其机制研究

项目名称： ZEB1-miR-300-FAK通路在肝癌上皮-间质转化中的作用及其机制研究

项目编号： No.81472258

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： 汪谦

作者单位： 中山大学

项目金额： 75万元

中文摘要： 上皮间质转化（EMT）是肝癌转移的重要始动环节。研究显示miRNA对EMT具有调控作用。我们前期发现miR-300低表达与肝癌EMT发生密切相关，但miR-300对肝癌EMT的作用及其自身低表达的分子机制不明？我们进一步发现：ZEB1转录因子可能通过作用于miR-300启动子下调其表达；miR-300可能再通过预测靶基因FAK抑制肝癌EMT。故我们推测：ZEB1通过抑制miR-300进而失去对FAK的作用促进肝癌EMT。为论证该假说，本项目拟通过体内外实验明确miR-300对肝癌EMT的作用；证实ZEB1 下调miR-300具体作用；阐明ZEB1-miR-300-FAK通路在肝癌EMT中的作用及机制；分析大量临床肝癌组织标本中ZEB1、miR-300、FAK与EMT的相关性；以及它们对肝癌临床病理和预后的意义。这将为确立miR-300作为抗肝癌EMT的早期诊断和靶点治疗提供可靠的科学依据。

中文关键词： C09_肝和肝内胆管肿瘤；肝癌；miR-300；上皮间质转化；ZEB1

英文摘要： Epithelial-mesenchymal transition (EMT) is an important part of the initiating stage of the metastasis in liver cancer. Studies have shown that miRNA's regulatory effect on EMT. We found that low expression of miR-300 is closely associated with EMT of the liver cancer, but the molecular mechanism of low expression of the miR-300 and its function to the EMT is still unknown? We further found that: ZEB1 transcription factor whose expression may be downregulated by its action to the miR-300 promoter; miR-300 may inhibit the liver cancer EMT by the predicting target genes FAK. Therefore we hypothesized that: ZEB1 through inhibition of miR-300 and then lost its action to FAK promotes EMT of the liver cancer. To prove this hypothesis, this project intends to define the role of miR-300 in liver cancer EMT by in vivo and vitro experiments; confirme the specific role that the ZEB1's downregulatory function to the miR-300; identify the ZEB1-miR-300-FAK pathway's mechanism and action of the EMT in HCC; analysis the correlation between ZEB1, miR-300, FAK and EMT in large scale clinical HCC specimens; liver cancer and their significance on clinicopathological and prognostic. This will provide a reliable scientific basis for establishing miR-300 as an anti-HCC EMT targets for early diagnosis and treatment.

英文关键词： ;hepatocellular carcinoma;miR-300;Epithelial -mesenchymal transition;zinc-finger E-box binding homeobox 1