摘要
目的通过生物信息学分析筛选出神经母细胞瘤外周血血浆外泌体中差异表达miRNA,并对其靶基因功能进行分析预测。方法从高通量基因表达数据库下载数据集GSE128004,分析神经母细胞瘤血浆外泌体中miRNA的差异表达;通过miRTarBase数据库筛选差异表达miRNA的靶基因;进一步通过运用clusterProfiler进行靶基因的基因本体(GO)功能富集与京都基因与基因组百科全书数据库(KEGG)通路富集。结果经筛选发现,数据集GSE128004包含41个表达差异在2倍以上的血浆外泌体miRNA。靶基因预测显示,hsa-miR-199a-3p, hsa-miR-196b-5p, hsa-miR-127-3p, hsa-miR-410-3p和hsa-miR-487b-3p为靶基因最多的前5个差异表达miRNA。GO功能分析发现,这些靶基因大都在细胞运动正调节、细胞迁移正调节、血管生成等生物过程富集;在膜侧、细胞-基底连接、细胞-基底黏附连接、焦点黏连等细胞组成富集;在蛋白丝氨酸/苏氨酸激酶活性、蛋白异二聚体化活性、转录因子活性和RNA聚合酶Ⅱ核心启动子近端区序列特异性结合等分子功能富集。KEGG分析显示:这些差异表达miRNA的靶基因主要参与磷脂酰肌醇3激酶-蛋白激酶B信号通路、癌症相关miRNA、丝裂原活化蛋白激酶信号通路等通路富集。结论 hsa-miR-199a-3p, hsa-miR-127-3p和hsa-miR-410-3p可能作为神经母细胞瘤的潜在生物标志物或治疗靶标,进一步为该病的发病机制提供研究思路。
Objective To screen the differently expressed miRNAs in plasma exosomes from peripheral blood of neuroblastoma by bioinformatics analysis for further study of their target genes.Methods The data set GSE128004 was downloaded from the high-throughput gene expression database,and the differential expression of miRNA in plasma exosomes of neuroblastoma was analyzed.The miRTarBase database was used to screen the target genes for differentially expressed miRNAs.The target genes were enriched Gene ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways by using clusterProfiler.Results It was found that the data set GSE128004 contains 41 plasma exosome miRNAs with more than two-fold difference in expression.The results of target gene prediction showed that the top five differentially expressed miRNA of target genes were hsa-miR-199 a-3 p hsa-miR-196 b-5 p,hsa-miR-127-3 p,hsa-miR-410-3 p,hsa-miR-487 b-3 p;GO enrichment analysis found that most of these target genes were enriched in biological processes such as positive cell movement regulation,positive cell migration regulation,and angiogenesis;enriched in cell component such as side of membrane,cell-basal junction,cell-basal adhesion junction,focal adhesion;the enriched molecular functions was mainly involved in protein serine/threonine kinase activity,protein heterodimerization activity,transcription factor activity,and sequence specific binding of the proximal region of the RNA polymeraseⅡcore promoter.KEGG analysis showed that these differentially expressed miRNA target genes were mainly involved in the enrichment of phosphatidylinositol 3-kinase-protein kinase B signaling pathway,cancer-related miRNA,mitogen-activated protein kinase signaling pathway.Conclusion This study suggested that hsa-miR-199 a-3 p,hsa-miR-127-3 p,hsa-miR-410-3 p might be potential biomarkers or therapeutic targets for neuroblastoma,providing research directions for the pathogenesis of the disease.
作者
杨威利
李瑞静
王潇娜
李纪同
张耀东
YANG Wei-li;LI Rui-jing;WANG Xiao-na;LI Ji-tong;ZHANG Yao-dong(Henan Key Laboratory of Children’s Genetics and Metabolic Diseases,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou 450018,Hennan Province,China;Henan Neurodevelopment Engineering Research Center for Children,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou 450018,Hennan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第7期891-894,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金青年科学基金资助项目(81901387)
河南省重点研发与推广专项课题资助项目(192102310074)
河南省医学科技攻关计划联合共建课题资助项目(LHGJ20190886)。
