[1]蒋光洁,陈燕华,郭维,等.急性T淋巴细胞性白血病关键基因的筛选与验证[J].南方医科大学学报,2018,(03):261.
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急性T淋巴细胞性白血病关键基因的筛选与验证()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年03期
页码:
261
栏目:
出版日期:
2018-04-03

文章信息/Info

Title:
Screening and verification of key genes in T-cell acute lymphoblastic leukemia
作者:
蒋光洁陈燕华郭维张航邹琳
关键词:
急性T淋巴细胞白血病生物信息学差异表达基因转录因子
Keywords:
T-cell acute lymphoblastic leukemia Bioinformatics analysis differentially expressed gene transcription factor
摘要:
目的筛选并验证急性T淋巴细胞性白血病关键基因,并对其进行生物信息学分析。方法从公共数据库基因表达数据库 (GEO)中下载T-ALL基因表达谱芯片GSE14317,应用R软件limma包筛选差异表达基因。利用DAVID数据库对差异基因进 行GO功能富集分析和KEGG通路富集分析,同时利用STRING数据库及Cytoscape软件构建差异蛋白互作网络,应用JASPAR 数据库构建转录因子靶基因网络,利用RT-PCR验证关键基因mRNA表达水平。结果GSE14317表达谱芯片中共有1443个差 异基因,包括800个上调基因和643个下调基因,这些差异基因主要富集在细胞周期,造血细胞系,细胞因子间相互作用以及T 细胞受体信号通路等。蛋白质相互作用网络图中显示节点最多的10 个枢纽基因分别是CDK1,PIK3R1,CCNB1,CCNA2, CDC20,JUN,GNG11,PLK1,PCNA和CCNB1,这些基因在子网络中分别富集于趋化因子信号通路,泛素介导的蛋白降解以及 细胞周期等。转录因子调节网络显示42个差异表达的转录因子,其中ELF5,HIC2和MEIS1与候选的9个关键基因启动子上游 均有结合位点。RT-PCR结果显示除GNG11外其余9个关键基因表达情况与芯片结果一致,ELF5,HIC2和MEIS1表达均升高 与芯片结果一致。结论CDK1,PIK3R1,CCNB1,CCNA2,CDC20,JUN,PLK1,PCNA,CCNB1,ELF5,HIC2 和MEIS1 在TALL 发生中发挥重要作用,为T-ALL的治疗和诊断提供生物学靶标。
Abstract:
Objective To explore the key genes in T-cell acute lymphoblastic leukemia (T-ALL) using bioinformatics method to better understand the pathogenic mechanisms of T-ALL. Methods The gene expression profiles of GSE14317 were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in T-ALL were analyzed using R package Limma. The online analysis tool DAVID was used to perform the functional and pathway enrichment analysis. The proteinprotein interaction network was constructed by STRING and visualized by Cytoscape. Based on the JASPAR database, the transcription factors (TFs) of the hub genes were obtained. RT-PCR was used to test the mRNA expression level of the key genes. Results A total of 1443 DEGs were identified, including 800 up-regulated genes and 643 down-regulated genes. These DEGs were significantly enriched in the cell cycle, hematopoietic cell lineage, cytokine-cytokine receptor interaction and T cell receptor signaling pathway. The top 10 hub genes identified from the PPI networks included CDK1, PIK3R1, CCNB1, CCNA2, CDC20, JUN, GNG11, PLK1, PCNA and CCNB2, which were enriched in chemokine signaling pathway, ubiquition mediated proteolysis and cell cycle. In the TF-target gene network, 42 differentially expressed TFs were identified, among which ELF5, HIC2 and MEISI had binding sites with 9 of the candidate hub genes. RT-PCR showed that the mRNA expression level of all the candidate hub genes except for GNG11 were consistent with the gene expression profiles. Conclusion The hub genes CDK1, PIK3R1, CCNB1, CCNA2, CDC20, JUN, PLK1, PCNA, CCNB2, ELF5, HIC2 and MEISI participate in the occurrence of TALL. Our finding provides new insights into the pathogenesis of T-ALL.

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更新日期/Last Update: 1900-01-01