Mir-134/487b/668基因簇与PTEN介导的信号通路在恶性纤维组织细胞瘤中的作用及机制研究

项目名称： Mir-134/487b/668基因簇与PTEN介导的信号通路在恶性纤维组织细胞瘤中的作用及机制研究

项目编号： No.81472512

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： 谷文光

作者单位： 哈尔滨医科大学

项目金额： 52万元

中文摘要： 恶性纤维组织细胞瘤（MFH）是一种病因不明的肿瘤。申请者前期研究发现MFH存在由14号染色体长臂转位形成的额外标记染色体；芯片分析显示mir134/487b/668 基因簇高表达且位于14号染色体长臂。文献证实mir-134/487b的靶基因是PTEN的支架蛋白MAGI2；mir-668的靶基因预测为PTEN，我们也发现PTEN在MFH呈低表达。据此提出以下假设：MFH由于14号染色体长臂转位形成额外染色体，可能导致位于其上的mir-134/487b/668基因簇高表达，靶向抑制支架蛋白MAGI2及PTEN基因，从而引发PTEN介导的多条信号通路异常，导致MFH的发生。针对假设申请者拟利用MFH细胞系，运用RNA干扰技术双向调节基因簇表达，检测MAGI2/PTEN信号网络变化，体内外观察MFH细胞功能变化，探讨mir-134/487b/668基因簇在MFH的功能及作用机制。

中文关键词： C19_间皮；软组织肿瘤；microRNA；基因簇；信号通路；RNA干扰

英文摘要： Malignant fibrous histiocytoma (MFH) is a soft tissue tumor of unknown etiology. In our preliminary study, we found that there was an extra marked chromosome in MFH cells, which were formed by chromosome 14q translocation; Microarray analysis showed mir134/487b/668 gene cluster showed high expression and they located in the long arm of chromosome 14. Literatures have confirmed that the target gene MAGI2 of mir-134/487b serves as scaffold protein of PTEN, and we also found that PTEN expression was low in MFH. We hereby put forward the following hypothesis: extra marked chromosome was formed by the long arm of chromosome 14 translocation, so mir-134/487b/668 gene cluster, which located in it, showed abnormal expression, its target gene MAGI2 inhibits expression of PTEN, so Triggering PTEN-induced signal pathway abnormalities, which can cause tumorigenesis. For the hypothesis, we use MFH cell line, RNA interferencing technology, transfect gene cluster fragments mimetics and inhibitors to MFH cells, detect MAGI2/PTEN signal networks changes, observe MFH cell function changes in vivo and in vitro, and find mir-134/487b/668 gene cluster function and mechanism on MFH.

英文关键词： malignant fibrous histiocytoma;microRNA;gene cluster;signaling pathway;RNA interference