MicroRNA363受甲基化调控与难治性弥漫大B细胞淋巴瘤相关机制的研究

项目名称： MicroRNA363受甲基化调控与难治性弥漫大B细胞淋巴瘤相关机制的研究

项目编号： No.81470365

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： 刘艳艳

作者单位： 郑州大学

项目金额： 70万元

中文摘要： MicroRNA363属于癌基因microRNA17-92家族的一员，前期研究发现它与弥漫大B细胞淋巴瘤免疫化疗治疗失败相关，通过靶基因CACNA1C影响利妥昔单抗诱导的钙离子内流和凋亡解释了部分治疗失败机制。本研究旨在进一步揭示microRNA363受甲基化调控与难治性弥漫大B细胞淋巴瘤相关的机制。前期研究显示microRNA363表达量与启动子甲基化程度呈负相关，生物信息学分析显示microRNA363高表达导致的治疗失败还与MAPK、Wnt癌基因通路活化有关。本研究利用基因芯片、免疫沉淀、病毒转染、移植鼠模型等多种方法，从体内和体外揭示①microRNA363受DNA甲基化调控的机制，以及去甲基化药物能否诱导治疗失败；②microRNA363高表达对癌基因通路影响的机制；③靶向癌基因通路药物对microRNA363耐药的逆转作用。通过研究最终发现克服耐药的方法。

中文关键词： 弥漫大B细胞淋巴瘤；DNA甲基化；microRNA363；癌基因信号通路

英文摘要： MicroRNA363 belongs to a member of oncogenic microRNA17-92 family. Our study has demonstrated its relation with treatment failure of diffuse large B cell lymphoma by immunochemothrapy, which was partly due to the effect of CACNA1C on rituximab-induced calcium influx and apoptosis. The project will further explore how microRNA363 is regulated by DNA methylation and associated with refractory behavior of diffuse large B cell lymphoma. Our preliminary study has revealed the control of microRNA363 expression by DNA methylation and activation of MAPK and Wnt pathways by it through bioinformation analysis.With many methods including gene array, immunoprecipitation，lentivirus transfection , mouse model, et al, we will confirm ①how microRNA363 is modulated by DNA methylation;②how microRNA363 activates oncogenic pathways;③if inhibitors of these oncogenic pathways can repress the growth of resistant lymphoma cells. Eventually, we expect to find novel approaches to overcome resistance.

英文关键词： diffuse large B cell lymphoma;DNA methylation;microRNA363;oncogenic pathway