调控Bmi-1基因的microRNAs分子群鉴定及其抑制骨髓瘤生长的研究

项目名称： 调控Bmi-1基因的microRNAs分子群鉴定及其抑制骨髓瘤生长的研究

项目编号： No.81201872

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 淋巴瘤及其他淋巴增殖性疾病

项目作者： 吴顺泉

作者单位： 福建医科大学

项目金额： 24万元

中文摘要： 癌基因Bmi-l与多种肿瘤的发生、发展密切相关，然而其高表达机制尚未明确。我们前期研究发现：Bmi-1在骨髓瘤中高表达，参与体外骨髓瘤细胞增殖、细胞周期的调控；且其表达可能受microRNAs调控。本研究拟对靶向调控Bmi-1的microRNAs进行全面系统的鉴定和功能学研究。首先将通过临床标本阐述骨髓瘤细胞Bmi-l表达及其临床意义；其次利用生物信息学预测和筛选能够作用于Bmi-1的microRNAs分子，并在骨髓瘤细胞中进行靶向作用及表达水平的验证，建立microRNAs-Bmi-l调控网络以阐明骨髓瘤中Bmi-l的调控机制；最后在骨髓瘤细胞中检测它们对肿瘤生物学行为的影响，确定骨髓瘤中能够调控Bmi-1且具有功能的microRNAs分子，进而研究它们在时间和空间上如何变化及对Bmi-1表达的影响和其在肿瘤演进中的作用，为骨髓瘤发病的分子机制提供实验依据，为疾病靶向治疗提供新靶标。

中文关键词： 骨髓瘤；Bmi-1；微小RNA；；

英文摘要： Oncogene Bmi-1 is closely related with tumorigenesis and development, yet the specific mechanism for overexpression of Bmi-1 remains largely unclear. Our preliminary studies showed that Bmi-1 was highly expressed in myeloma and participated in regulating the cell growth and cell cycle of myeloma cells in vitro. Meanwhile, we have found that Bmi-1 might be post-transcriptionally regulated by microRNAs in myeloma. In this study, we will screen and identify microRNAs which can directly target Bmi-1 and explore the biological function and significance of these microRNAs comprehensively and systematically. Firstly expression and clinic significance of Bmi-1 in myeloma will be investigated in clinic samples. Then, we will screen out the microRNAs reversely which maybe involved in Bmi-1 post-transcriptional regulation by using bioinformatic prediction, identify their expression and function experimentally, establish the regulation network between microRNAs and Bmi-1, and elucidate the regulation mechanism of Bmi-1 in myeloma. The biological function of these microRNAs will finally be illuminated emphatically, further their roles on Bmi-1 expression and tumor progression temporally and spatially will be investigated. Hope this study will provide the experiment evidence to further understanding the molecular mechanism

英文关键词： multiple myeloma；Bmi-1；microRNA；；