CDKN2B-AS may indirectly regulate coronary artery disease-associated genes via targeting miR-92a
CDKN2B-AS may indirectly regulate coronary artery disease-associated genes via targeting miR-92a
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DOI：
10.1016/j.gene.2017.07.070
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发表时间：
2017-09-20
期刊：
影响因子：
3.5
通讯作者：
Li, Junquan
中科院分区：
文献类型：
--
作者：
Cheng, Ming;An, Shoukuan;Li, Junquan
目的：冠状动脉疾病（CAD）具有高死亡率，并且由多种病症组成，包括稳定/不稳定型心绞痛、心源性猝死和心肌梗死。方法：从GeneExpressionOmnibus数据库中获取GSE 20680（包括87例CAD患者和52例正常人）和GSE 20681（包括99例CAD患者和99例正常人）的基因数据集。采用MetaDE技术对差异表达基因进行鉴定。在MetaDE软件包中对效应大小进行聚类分析，然后在R.利用miR 2Disease和miRTarBase数据库分别获得CAD相关microRNA（miRNAs）及其靶基因，并基于BioGRID、HPRD和DIP数据库构建相关miRNA-DEG调控网络。利用Fisher精确检验对所涉及的DEG进行富集分析，并构建支持向量机（SVM）分类器以优化特征基因。结果：共筛选出1208个DEG，预测出5个CAD相关的miRNA（包括miR-92 a）。基于41个特征基因构建的SVM分类器具有较高的识别效率。仅获得一个靶向miR-92 a的IncRNA CDKN 2B-AS。结论：CDKN 2B-AS通过miR-92 a间接调控GATA 2、1VIAP 1B和ARG 1参与CAD的发生。
Objective: Coronary artery disease (CAD) has a high mortality rate and consists of multiple condition, including stable/unstable angina, sudden cardiac death, and myocardial infarction. This study is aimed to explore the pathogenesis of CAD.Methods: Datasets of GSE20680 (including 87 CAD samples and 52 normal samples) and GSE20681 (including 99 CAD samples and 99 normal samples) were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by MetaDE. Effect Sizes in MetaDE package, and then were hierarchical clustered using pheatmap package in R. Subsequently, CAD-associated microRNAs (miRNAs) and their targets were obtained separately by miR2Disease and miRTarBase databases, and then used to construct an associated-miRNA-DEG regulatory network based on BioGRID, HPRD and DIP databases. Enrichment analysis was conducted for the involved DEGs using Fisher's exact test, and a support vector machine (SVM) classifier was constructed to optimize the feature genes. After CAD-associated long non-coding RNAs (IncRNAs) were predicted by IncRNA Disease database and their target miRNAs were predicted using miRcode and starBase databases, IncRNA-miRNA-DEG regulatory network was constructed.Results: Total 1208 DEGs were screened, and 5 CAD-associated miRNAs (including miR-92a) were predicted associated with CAD. The SVM classifier was constructed based on the 41 featured genes and had high recognition efficiency. Only one IncRNA CDKN2B-AS targeting miR-92a was obtained. Finally, GATA2, MAP1B and ARG1 were involved in the CDKN2B-AS miR-92a-feature gene regulatory network.Conclusion: GATA2, 1VIAP1B and ARG1 indirectly regulated by CDKN2B-AS through miR-92a might be involved in CAD.