S100A4-miR155在肝癌组织间充质干细胞调控肝癌增殖及转移中的作用及机制研究

项目名称： S100A4-miR155在肝癌组织间充质干细胞调控肝癌增殖及转移中的作用及机制研究

项目编号： No.81201874

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： 阎新龙

作者单位： 中国科学院遗传与发育生物学研究所

项目金额： 23万元

中文摘要： 间充质干细胞（MSC）是肿瘤微环境的重要组成部分之一，在肿瘤发生发展中发挥重要作用。我们的预实验表明：（1）肝癌组织存在MSC，其能促进肝癌增殖和转移；（2）cDNA表达谱芯片提示肝癌MSC高表达S100A4，且S100A4高表达促进肝癌增殖和转移；（3）共培养实验表明MSC显著上调肝癌细胞中miR155的表达，外源高表达S100A4促进肝癌miR155的表达，初步建立了肝癌MSC中S100A4与肝癌细胞miR155上调的联系。在此基础上，我们推测"S100A4-miR155在肝癌组织MSC促进肝癌增殖及转移中发挥重要作用"。为证实该假说，将应用RNAi、miR155高表达和抑制表达、生物信息学分析、荧光素酶报告系统、Western blot、裸鼠皮下成瘤、肝内转移模型等进行验证。本研究从新的视角探讨肝癌MSC微环境如何参与调控肝癌细胞miRNA的表达，以期为肝癌的微环境干预提供新的靶点。

中文关键词： 间充质干细胞；肝癌；转移；miR-155；S100A4

英文摘要： Mesenchymal stem cells are one of the important parts of tumor stroma ,and they play a critical role in promoting cancer progression.Our preliminary results demonstrated that there was the presence of MSCs in hepatocarcinoma tissues and they could promote hepatocarcinoma cells proliferation and metastasis in vivo. Next,the cDNA expression microarray showed that S100A4 was highly expressed in hepatocarcinoma associated MSCs,and exterior expression of the S100A4 vector in hepatocarcinomal cell lines could promote cancer proliferation and metastasis.Furthermore, we found that the miR155 expression in hepatocarcinoma cells was significantly upregulated after been cocultured with the hepatocarcinoma associated MSCs.and the S100A4 overexpression in hepatocarcinomal cell lines could up-regulate the expression of miR155 ,our results suggest that there may be a close tie between the expression of S100A4 and miR155. On the basis of the above results, we propose the hypothesis that the axis of S100A4-miR155 might play a pivatal role of hepatocarcinoma associated MSCs in modulating cancer proliferation and metastasis.To verify the hypothesis ,our project will utilize the methods of RNAi,the gain and loss of function of miR155,downstream target genes predicted by targetScan,dual luciferase reporter system, western blot,tumor

英文关键词： mesenchymal stem cells；hepatocarcinoma；metastasis；miR-155；S100A4