LncRNA-00941在肝癌间充质干细胞调控肿瘤干细胞自我更新中的作用及机制研究

项目名称： LncRNA-00941在肝癌间充质干细胞调控肿瘤干细胞自我更新中的作用及机制研究

项目编号： No.81472341

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： 阎新龙

作者单位： 北京工业大学

项目金额： 90万元

中文摘要： 肝癌组织微环境中的间充质干细胞（MSC）如何调控肝癌干细胞（CSC）的功能尚未明了。近年来，长链非编码RNA（lncRNA）在肿瘤发生发展中的作用日益被重视，那么lncRNA是否参与肝癌MSC调控肿瘤干细胞的功能呢？我们发现肝癌MSC促进肝癌转移，在此基础上，我们进一步证明肝癌MSC促进肿瘤球（sphere）增殖和增加CSC的比例, 且肝癌MSC促进肿瘤梯度稀释后肝癌形成及体内转移。lncRNA芯片发现lncRNA-00941在MSC处理的肝癌细胞高表达，在肝癌CSC球及肝癌标本高表达，我们推测lncRNA-00941可能在肝癌MSC调控肿瘤CSC自我更新中发挥重要作用。为此，本项目将从MSC微环境的视角探讨lncRNA-00941如何调控肝癌CSC的自我更新及分子机制，鉴定肝癌MSC分泌的细胞因子如何参与lncRNA-00941的表达及相应的干预策略，以期为肝癌微环境干预提供新的靶点

中文关键词： C09_肝和肝内胆管肿瘤；间充质干细胞；肿瘤干细胞；lncRNA；自我更新

英文摘要： Whether liver cancer associated mesenchymal stem cells (LC-MSCs) can modulate liver cancer stem cells remains unclear. Recently, more and more lncRNAs are found playing pivotal roles in tumor ontogenesis. Whether lncRNAs can particapate in mesenchymal stem cell microenvironment regualting liver cancer stem cell or not is still an open question. Our previous research demonstrated that LC-MSCs significantly promoted hepatocellular carcinoma metastasis. Based on these results, we further found that LC-MSCs promoted the proliferation of liver tumor sphere and enhanced the surface marker of cancer stem cells. In the limiting dilution analysis, LC-MSCs enhanced tumor formation and tumor metastasis in vivo.Through the lncRNA microarray analysis, we identify that lncRNA-00941 was significantly upregualted in HCC cells by LC-MSCs coculture. It was also highly expressed in liver cancer stem cells and HCC samples. Based on these above results, we propose the hypothesis that lncRNA-00941 may play an important role in LC-MSCs modulating the self-renewal of liver cancer stem cells. To verify this hypothesis, we will explore the role and mechanism of lncRNA-00941 in LC-MSCs regulating liver cancer stem cells self-renewal and to find which cytokine secreted from LC-MSCs can upregulate the expression of lncRNA-00941, and to optimize the intervention strategies.The deep understanding of the lncRNA's role in the crosstalk between MSC niche and liver cancer stem cells will provide new targets for HCC therapy.

英文关键词： hepatocarcinoma and intrahepatic cholangiocarcinoma;mesenchymal stem cells;cancer stem cells;lncRNA;self-renewal