miR-150在急性髓细胞白血病中的表达和功能研究

项目名称： miR-150在急性髓细胞白血病中的表达和功能研究

项目编号： No.81200364

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 方志鸿

作者单位： 厦门大学

项目金额： 23万元

中文摘要： miRNAs是一类小分子的非编码RNAs，其表达变化与急性髓细胞白血病（AML）特定的遗传学改变和预后相关，在AML发病机制中起重要调控作用。miR-150是造血和免疫系统的一个关键调节因子，我们前期研究发现它在AML显著低表达，外源性miR-150明显抑制白血病细胞的活性,并激活caspase3启动细胞凋亡,但机制尚不清楚。我们推测miR-150表达下调或缺失是AML遗传学改变的一个关键事件，通过调控相关基因和信号参与AML的发生发展。本项目拟通过检测AML患者miR-150表达水平并分析与特定遗传学改变和预后的关系，同时在细胞和动物模型上验证miR-150对白血病细胞生长和致瘤能力的抑制作用，应用差异基因表达分析、荧光素酶报告系统等手段预测和确证miR-150的关键靶基因及相关信号调节通路，阐明miR-150在AML中的作用和分子机制，为以miR-150为靶点的生物学治疗提供理论依据。

中文关键词： 白血病；miR-150；肿瘤抑制因子；信号通路；生物治疗

英文摘要： Expression of miRNAs, a new class of small noncoding RNAs，has been demonstrated to be altered in acute myeloid leukemia(AML) and associated with specific cytogenetic subsets and prognostic relevance. Changes in the expression of several miRNAs altered in AML have been shown to have functional relevance in leukemogenesis. We have found that miR-150,an important regulator in hematopoiesis and immune system, is down-regulated in AML. Restoration of miR-150 in AML cell lines dramatically inhibits cell growth，and initiates caspase3 activtion,leading to cell death through unknown mechanisms. Therefore, we presumed that miR-150 might play important roles in pathogenesis and disease progression in AML. In this study, we will analyze the probability correlation of miR-150 expression with specific cytogenetic subsets and prognostic significance of AML. Then, the hypothesis that exogenous expression of miR-150 can inhibit leukemia cell growth and reduce tumorigenicity will be verified in vitro as well as in a xenograft leukemia animal model. Microarray and luciferase assays will be used to predict and validate its targets. Finally, we carry out GO categories to functional annotation analysis of these predicted targets and their involvement in biological processes as well as signaling pathways. Together, our research will h

英文关键词： leukemia；miR-150；tumor suppressor；signal transduction；biologic therapy