Li Jie, Qin Yi, Zhang Haiyan
Department of Transfusion Medicine, The Fifth Central Hospital of Tianjin, Tianjin 300450, P.R. China.
Institute of Medical Laboratory, Tianjin Medical University, Tianjin 300072, P.R. China.
Oncol Lett. 2018 Jan;15(1):361-367. doi: 10.3892/ol.2017.7287. Epub 2017 Oct 30.
The aim of the present study was to explore the miRNA-Gene regulatory mechanism in chronic lymphocytic leukemia (CLL), and identify new targets for the therapy of CLL. The miRNA expression dataset GSE62137 and mRNA expression dataset GSE22529 were downloaded from National Center of Biotechnology Information Gene Expression Omnibus database. In CLL samples compared with normal B cell samples, differentially expressed miRNAs (DEMs) were identified via the GEO2R instrument of GEO and differentially expressed genes (DEGs) were obtained via the limma package of . Functional enrichment analysis of the DEGs was performed via the Database for Annotation, Visualization and Integrated Discovery. The targets of the DEMs were identified based on the miRNAWalk platform. The overlaps between the DEGs and the targets of the DEMs were selected, and the miRNA-Gene regulatory network was constructed based on the overlaps and the corresponding DEMs. A total of 63 DEMs and 504 DEGs were identified in CLL samples compared with normal B cell samples. Eleven enriched functional clusters of the DEGs were obtained. 405 miRNA-Gene regulatory pairs were identified. The miRNA-Gene regulatory pairs contained 351 target genes of the DEMs, including 9 overlaps with the DEGs. A miRNA-Gene regulatory network was constructed. Bioinformatics methods could help us develop a better understanding of the molecular mechanism of CLL. MiRNAs may play a critical role in regulating the process of CLL. They may affect CLL by regulating the processes of immunoreactivity and protein degradation. Genes such as Neurogenic Locus Notch Homolog Protein 2, PR/SET domain 4 and A-kinase anchoring protein 12 may be their regulating targets in CLL.
本研究的目的是探索慢性淋巴细胞白血病（CLL）中的miRNA-基因调控机制，并确定CLL治疗的新靶点。从美国国立生物技术信息中心基因表达综合数据库下载了miRNA表达数据集GSE62137和mRNA表达数据集GSE22529。在CLL样本与正常B细胞样本的比较中，通过GEO的GEO2R工具鉴定差异表达的miRNA（DEM），并通过R语言的limma软件包获得差异表达基因（DEG）。通过注释、可视化和综合发现数据库对DEG进行功能富集分析。基于miRNAWalk平台鉴定DEM的靶标。选择DEG与DEM靶标之间的重叠部分，并基于重叠部分和相应的DEM构建miRNA-基因调控网络。与正常B细胞样本相比，在CLL样本中总共鉴定出63个DEM和504个DEG。获得了DEG的11个富集功能簇。鉴定出405个miRNA-基因调控对。这些miRNA-基因调控对包含351个DEM的靶基因，其中9个与DEG重叠。构建了一个miRNA-基因调控网络。生物信息学方法有助于我们更好地理解CLL的分子机制。miRNA可能在调节CLL进程中起关键作用。它们可能通过调节免疫反应和蛋白质降解过程来影响CLL。神经源位点Notch同源蛋白2、PR/SET结构域4和A激酶锚定蛋白12等基因可能是它们在CLL中的调控靶点。
