| 组蛋白去甲基化酶KDM3B在急性髓系白血病中的靶基因鉴定 |
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| 引用本文： | 宋 磊,徐 鑫,赵 瑶,王占聚,胡振波.组蛋白去甲基化酶KDM3B在急性髓系白血病中的靶基因鉴定[J].现代肿瘤医学,2018,0(8):1149-1154. |
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| 作者姓名： | 宋 磊 徐 鑫 赵 瑶 王占聚 胡振波 |
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| 作者单位： | 1.潍坊医学院，山东 潍坊 261042;
2.潍坊医学院附属医院干细胞与再生医学实验室；3.血液科， 山东 潍坊 261042 |
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| 基金项目： | Natural Science Foundation of China（No.81570157);国家自然科学基金(编号:81570157);山东省医药卫生科技发展计划(编号:2013WS0291) |
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| 摘 要： | 目的:组蛋白H3赖氨酸9位（H3K9）的甲基化是造血和白血病发生中关键的表观遗传学修饰，由组蛋白甲基化酶和去甲基化酶精确调控。组蛋白H3K9去甲基化酶KDM3B则是一个潜在的白血病发生抑制基因。我们旨在探讨白血病中KDM3B的潜在靶基因。方法:干涉多个急性髓系白血病细胞株中的KDM3B基因后进行微阵列芯片实验，采用基因集富集分析（GSEA）及Venn分析数据，筛选出若干KDM3B潜在的靶基因，并用实时定量PCR对CDKN1A基因的结果进行验证。结果:对比GSEA 的分子标签数据库中标志基因集（H）和已建立的基因集(C2)，在NB-4和PLB-985细胞中（分别影响），与KDM3B正相关的基因分别有2 375和2 007个，其中P＜0.05的基因分别有89和67个;与KDM3B负相关的基因分别有1 882和2 250个，其中P＜0.05的基因分别有62和67个，包括FLT3、NRAS、EVI1和IL4等基因。对比GSEA 的分子标签数据库中染色体位置（C1）、已建立的基因集（C2）、模序（C3）、肿瘤相关基因集（C4）、GO 基因集（C5）、致瘤基因集（C6）、免疫学基因集（C7）和标志基因集（H）,在NB-4和PLB-985细胞中（共同影响），与KDM3B正相关的基因有4 815个，其中P＜0.05的基因有130个;与KDM3B负相关的基因有4 400个，其中P＜0.05的基因有97个，包括POU5F1和CDKN1A等基因。干扰NB-4和PLB-985细胞中KDM3B基因的表达，我们选取影响最强的600个探针用Venn分析，在两种细胞系中表达均下降的基因有16个，包括血液病相关基因CCDN3、TRIM24、MAPKI3、SOX6等；在NB-4细胞中表达降低但在PLB-985细胞中表达升高的基因有17个，包括RARRES3和CD58等基因。实时定量PCR结果显示干扰PLB-985细胞中KDM3B后CDKN1A的表达是对照组的1.18倍。结论:KDM3B调控急性髓系白血病相关基因，CDKN1A是一个潜在的KDM3B靶基因。
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| 关 键 词： | 急性髓系白血病 表观遗传学 组蛋白去甲基化酶 KDM3B 微阵列芯片 基因集富集分析 |
Identification of the histone demethylase KDM3B target gene in acute myeloid leukemia |
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| Song Lei,Xu Xin,Zhao Yao,Wang Zhanju,Hu Zhenbo.Identification of the histone demethylase KDM3B target gene in acute myeloid leukemia[J].Journal of Modern Oncology,2018,0(8):1149-1154. |
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| Authors: | Song Lei Xu Xin Zhao Yao Wang Zhanju Hu Zhenbo |
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| Affiliation: | 1.Weifang Medical University,Shandong Weifang 261042，China;2.Laboratory of Stem Cell and Regenerative Medicine;3.Department of Hematology,Affiliated Hospital of Weifang Medical University，Shandong Weifang 261042，China. |
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| Abstract: | Objective:Histone H3 lysine 9（H3K9) methylation is the key epigenetic modification in hematopoiesis and leukemia,and is regulated by histone methylase and demethylase.Histone H3K9 demethylase KDM3B is a potential leukemia suppressor gene.We aimed to investigate the target gene of KDM3B in leukemia.Methods:Microarray analysis was performed on multiple acute myeloid leukemia cell lines after intervention of KDM3B,and the results were verified by Real-time quantitative PCR.Results:Compared with the gene set hallmark(H) and curate(C2) in the molecular tag database of the GSEA,2 375 and 2 007 genes were positively correlated with KDM3B in NB-4 and PLB-985 cells,among which 89 and 67 were P＜0.05,1 882 and 2 250 negative genes associated with KDM3B,of which 62 and 67 were P＜0.05,including FLT3,NRAS and EVI1,IL4 genes.Compared with the gene set position(C1),curate(C2),motif(C3),computational(C4),gene ontology(C5),oncogenic signatures(C6),immunologic signatures(C7) and hallmark(H),in the NB-4 cells and PLB-985 cells,there were 4 815 genes were positively correlated with KDM3B,among which there were 130 genes with P＜0.05.4 400 genes were negatively correlated with KDM3B,and 97 genes were P＜0.05,including POU5F1 and CDKN1A and so on.To investigate the expression of gene in NB-4 and PLB cells,we elected 600 of the most influential probes with Venn analysis,and 16 genes were down-regulated in both cell lines,including blood cell related genes CCDN3,TRIM24,MAPKI3,SOX6 and 17 genes reduced expression in NB-4 cells but up-expressed in PLB-985 cells,including RARRES3 and CD58.Real-time quantitative PCR results showed that the expression of CDKN1A was 1.18 times higher than that of normal cells after interfering with KDM3B in PLB-985 cells.Conclusion:KDM3B regulates acute myeloid leukemia-associated genes,and CDKN1A is a potential KDM3B target gene. |
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| Keywords: | AML epigenetics histone demethylases KDM3B microarray GSEA |
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