长链非编码RNA HOTAIR参与调控t(8;21)+白血病细胞的分化及其机制研究

项目名称： 长链非编码RNA HOTAIR参与调控t(8;21)+白血病细胞的分化及其机制研究

项目编号： No.31201033

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 李小雷

作者单位： 中国人民解放军总医院

项目金额： 23万元

中文摘要： 摘要 我们前期研究发现长链非编码RNA HOTAIR在t(8;21)+的急性髓系白血病中特异性的表达缺失，生物信息学显示HOTAIR启动子区存在有保守的AML1结合位点，前期实验初步证明AML1-ETO通过竞争抑制AML1活性调控HOTAIR的表达。鉴于此，我们提出在t(8;21)+白血病中AML1-ETO通过抑制HOTAIR的表达参与白血病细胞分化调控,基于前期发现，本项目将：1）运用分子生物学、细胞培养等相关技术，从细胞水平研究t(8;21)+白血病细胞中HOTAIR的表达调控机制及它的异位表达对白血病细胞分化的影响；2）运用基因芯片等技术挖掘HOTAIR参与白血病细胞分化的下游关键分子，从而揭示HOTAIR参与的分子信号调控途径在白血病发生的重要作用；3）采用细胞原位杂交等方法研究HOTAIR在不同的AML分型、分期病人标本中的表达情况，揭示它们之间的关联性以及与白血病进展的关系。

中文关键词： 长链非编码RNA；HOTAIR；肿瘤治疗抵抗；侵袭；转移

英文摘要： Abstract Our previous studies have found that the expression of lncRNA HOTAIR was specific absence in human acute myeloid leukemia(AML) cells with the (8;21)(q22;q22) chromosomal translocation,which involves AML1 gene on chromosome 21 and the ETO gene on chromosome 8, generates an AML1/ETO fusion.We also performed bioinformatics predication.The results of predication have indicated that the promoter region of HOTAIR exist several conserved AML1 binding sites.Firstly,we indicated that the AML1-ETO fusion gene could inhibit HOTAIR expression via competing with the transcriptional activation of AML1 by luciferase reporter arrays.HOTAIR is one gene whose expression is highly negative correlated with the presence of the AML1-ETO fusion. Therefore, we propose that the AML1-ETO acts as a dominant negative inhibitor of AML1 and represses the expression of HOTAIR invoved in leukemia cells differentiation.Based on our preliminary findings and the fact that AML1-ETO could act as a transcriptional repressor for HOTAIR of AML1 target gene. We propose the project and play to perfrom it as follow: 1) molecular biology, cell culture and other related-technologies will be performed in our study, from cell line level, we will investigate the regulation mechanisms of HOTAIR and ectopic expression of HOTAIR in leukemia cells with

英文关键词： long noncoding RNA；HOTAIR；tumor therapy resistant；invasion；metastasis