miR-759在原发性肝细胞癌恶性进展中的分子功能和网络调控机制及其潜在的治疗作用

项目名称： miR-759在原发性肝细胞癌恶性进展中的分子功能和网络调控机制及其潜在的治疗作用

项目编号： No.81201971

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： 郑芳

作者单位： 中山大学

项目金额： 25万元

中文摘要： 预实验发现，miR-759在HCC细胞系和血浆中表达明显下调，且与HCC的侵袭转移相关。但miR-759异常在HCC恶性进展中的分子致癌特征和相关的网络调节机制还不清楚。 本项目拟应用分子肿瘤学研究方法和高通量检测技术，检测正常人和HCC病人组织、血浆中的miR-759表达，分析miR-759表达水平与HCC转移的相关性；分别探讨miR-759对HCC细胞骨架、丝状伪足、板状伪足、直线运动、EMT和肿瘤血管形成、动物体内肿瘤转移等生物学行为的影响；确定HCC中miR-759作用的靶基因和重要的下游转移相关基因；明确miR-759作用的靶基因异常表达的信号转导通路及其在HCC恶性进展中的临床肿瘤学意义。然后采用动物转移瘤模型，探讨miR-759对HCC体内转移的潜在治疗效果；深入研究miR-759在HCC发生发展中表达失调的分子网络机制，致力为全面认识HCC的分子遗传学特征提供实验研究的依据

中文关键词： 非编码RNA；肝细胞癌；转移；分子调节网络；

英文摘要： It has been demonstrated that the development of Hepatocellular Carcinoma (HCC) has been accompanied by the multiple-molecular changes and the multiple-step complicated process. It has been reported that altered microRNA expression plays the important role in HCC aggressive progression. Recently, we found that the expression of miR-759 was significantly down-regulated in HCC cell lines and plasma of patient with metastasis. So maybe the low expression of miR-759 has associated with the invasion and metastasis of HCC . However, it has been unknown for the molecular carcinogenic character and relative regulating network mechanisms of miR-759 disregulation in HCC aggressive progression. We will examine the expression of miR-759 in the tissue and plasma of normal and HCC patients by the use of associated molecular oncological study methods and high-output detection technology and analyze the correlation between the expression levels of miR-759 and HCC clinical pathological parameters. In addition, we will explore the effect of the overexpression of miR-759 in HCC cell lines on the tumor biological behaviour, such as the formation of stress fiber, filopodial, lamellipodial,directional movement,epithelial-mesenchymaltransition, migration, invasion and tumor angiogenesis and in vivo tumor metastasis. All the mor

英文关键词： non-coding RNA；HCC；metastasis；molecular modulatory network；