MicroRNA-379调控FAK在肝癌侵袭转移中的作用及机制研究

项目名称： MicroRNA-379调控FAK在肝癌侵袭转移中的作用及机制研究

项目编号： No.81201930

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 陈劲松

作者单位： 广州医科大学

项目金额： 23万元

中文摘要： 我们已证实FAK(局部粘着斑激酶)在肝癌侵袭转移中发挥重要作用。但是，肝癌中靶向调控FAK的microRNA（miR）及作用尚不清楚。前期，我们通过microRNA芯片发现miR-379 在肝癌组织中表达明显下调，且生物信息学方法预测FAK是miR-379的直接靶基因；进一步研究显示在肝癌细胞中过表达miR-379可显著下调FAK蛋白表达，同时细胞的迁移侵袭能力明显下降。由此，我们提出miR-379通过靶向调控FAK抑制肝癌侵袭转移。本项目拟采用基因转染、定量PCR、Western-blot、报告基因、动物模型、原位杂交、免疫组化等方法，旨在获得miR-379通过调控FAK抑制肝癌侵袭转移的可靠证据并阐明其分子机制。本项目不仅有助于阐明肝癌的侵袭转移机制，为预测肝癌转移复发提供新的生物标志物，且为确立miR-379作为抗肝癌转移治疗的新靶点提供充分的科学依据。

中文关键词： 肝细胞癌；微小RNA-379-5p；局部黏着斑激酶；转移；上皮间质转化

英文摘要： We have demonstrated that focal adhesion kinase (FAK) plays an important role in invasion and metastasis of hepatocellular carcinoma (HCC). However, the roles of microRNA (miR) targeting FAK remain unclear in HCC. In preliminary studies, we found that miR-379 expression was significantly downregulated in HCC tissues by microRNA microarray. Furthermore, FAK is predicted to be the direct target of miR-379 by bioinformatics methods. Moreover, our studies showed that forced expression of miR-379 significantly downregulated FAK protein expression and suppressed cell migration and invasion in HCC cells. Thus, we propose that miR-379 suppresses invasion and metastasis of HCC by targeting FAK. This study aims to confirm that miR-379 suppresses invasion and metastasis of HCC by targeting FAK and to elucidate its underlying molecular mechanisms through gene transfection, quantitative reverse transcription polymerase chain reaction, western-blot, luciferase reporter gene assay, animal model, in situ hybridization, immunohistochemistry, etc. Taken together, this study will help elucidate the mechanisms underlying invasion and metastasis of HCC, provide a novel biomarker for predicting metastasis and recurrence of HCC, and provide enough scientific evidence to establish miR-379 as a novel target for antimetastatic therapy

英文关键词： Hepatocellular carcinoma；microRNA-379-5p；Focal adhesion Kinase；Metastasis；Epithelial-to-mesenchymal transition