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基于生物信息学分析鉴定急性髓系白血病潜在治疗靶点基因、关键微小RNA及机制

Identification of potential therapeutic target genes, key miRNAs and mechanisms in acute myeloid leukemia based on bioinformatics analysis.

作者信息

Zhao Yanhong, Zhang Xuefang, Zhao Yanqiu, Kong Desheng, Qin Fan, Sun Jing, Dong Ying

机构信息

Department of Hematology, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, 150001, China,

出版信息

Med Oncol. 2015 May;32(5):152. doi: 10.1007/s12032-015-0572-4. Epub 2015 Apr 2.

Abstract

The study was aimed to explore the underlying mechanisms and identify the potential target genes and key miRNAs for acute myeloid leukemia (AML) treatment by bioinformatics analysis. The microarray data of GSE9476 were downloaded from Gene Expression Omnibus database. A total of 64 samples, including 26 AML and 38 normal samples, were used to identify differentially expressed genes (DEGs) between AML and normal samples. The functional enrichment analysis was performed, and protein-protein interaction (PPI) network of the DEGs was constructed by Cytoscape software. Besides, the target miRNAs for DEGs were identified. Totally, 323 DEGs were identified, including 87 up-regulated and 236 down-regulated genes. Not only up-regulated genes but also down-regulated genes were related to hematopoietic-related functions. Besides, down-regulated genes were also enriched in primary immunodeficiency pathway. Tumor necrosis factor (TNF), interleukin 7 receptor (IL7R), lymphocyte-specific protein tyrosine kinase (LCK), CD79a molecule and immunoglobulin-associated alpha (CD79A) were identified in these functions. TNF and LCK were hub nodes in PPI networks. miR-124 and miR-181 were important miRNAs in this study. The hematopoietic-related functions and primary immunodeficiency pathway may be associated with AML development. Genes, such as TNF, IL7R, LCK and CD79A, may be potential therapeutic target genes for AML, and miR-124 and miR-181 may be key miRNAs in AML development.

摘要

本研究旨在通过生物信息学分析探索急性髓系白血病(AML)治疗的潜在机制,并鉴定潜在的靶基因和关键微小RNA(miRNA)。从基因表达综合数据库下载了GSE9476的微阵列数据。共使用64个样本,包括26个AML样本和38个正常样本,以鉴定AML样本与正常样本之间的差异表达基因(DEG)。进行了功能富集分析,并通过Cytoscape软件构建了DEG的蛋白质-蛋白质相互作用(PPI)网络。此外,还鉴定了DEG的靶miRNA。总共鉴定出323个DEG,包括87个上调基因和236个下调基因。上调基因和下调基因均与造血相关功能有关。此外,下调基因还富集于原发性免疫缺陷途径。在这些功能中鉴定出肿瘤坏死因子(TNF)、白细胞介素7受体(IL7R)、淋巴细胞特异性蛋白酪氨酸激酶(LCK)、CD79a分子和免疫球蛋白相关α(CD79A)。TNF和LCK是PPI网络中的枢纽节点。miR-124和miR-181是本研究中的重要miRNA。造血相关功能和原发性免疫缺陷途径可能与AML的发生发展有关。TNF、IL7R、LCK和CD79A等基因可能是AML潜在的治疗靶基因,而miR-124和miR-181可能是AML发生发展中的关键miRNA。

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