Bioinformatical Analysis of miRNA-mRNA Interaction Network Underlying Macrophage Aging and Cholesterol-Responsive Difference between Young and Aged Macrophages
Bioinformatical Analysis of miRNA-mRNA Interaction Network Underlying Macrophage Aging and Cholesterol-Responsive Difference between Young and Aged Macrophages
复制标题
巨噬细胞衰老背后的 miRNA-mRNA 相互作用网络以及年轻和老年巨噬细胞之间胆固醇反应差异的生物信息分析
DOI：
10.1155/2020/9267475
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发表时间：
2020-06-13
影响因子：
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通讯作者：
Lu，Peirong
中科院分区：
文献类型：
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作者：
Li，Jianqing;Yin，Xue;Lu，Peirong
目的巨噬细胞衰老参与年龄相关性黄斑变性（AMD）的发生和发展。本研究的目的是通过生物信息学分析，鉴定巨噬细胞衰老和对胆固醇反应的特异性microRNAs （miRNA）、mrna及其相互作用，从而更好地了解AMD的机制。方法从Gene Expression Omnibus（登录号GSE111304和GSE111382）获取微阵列数据。利用R软件鉴定巨噬细胞中年龄相关的差异表达基因。通过miRWalk、mirTarBase、starBase进一步分析miRNA-mRNA相互作用，然后由Cytoscape产生。通过DAVID和STRING数据库对miRNA靶基因的Gene Ontology和KEGG通路进行功能标注。此外，构建了蛋白-蛋白相互作用网络，以确定响应外源胆固醇的关键基因。结果老龄巨噬细胞与年轻巨噬细胞比较，共检测到14种mirna和101种mrna的差异表达。此外，检测到19个验证的miRNA-mRNA相互作用和544个预测的miRNA-mRNA相互作用。通过对miRNA靶点的功能注释，发现脂质代谢过程与巨噬细胞衰老有关。在氧化和乙酰化的低密度脂蛋白处理后，miR-714和16 mrna在老年和年轻巨噬细胞中对两种胆固醇的响应差异表达。其中检测到6对miRNA-mRNA预测对。功能注释主要与脂质代谢过程有关，并确定了法尼基二磷酸法尼基转移酶1 （FDFT1）是老年和年轻巨噬细胞对胆固醇反应差异的关键基因。结论脂质代谢过程在巨噬细胞衰老和对胆固醇的反应中都起关键作用，因此被认为与AMD的发生和发展有关。此外，miR-714-FDFT1可能调节衰老巨噬细胞中的胆固醇稳态，并有可能成为AMD的新治疗靶点。
Purpose Macrophage aging is involved with the occurrence and progression of age-related macular degeneration (AMD). The purpose of this study was to identify the specific microRNAs (miRNA), mRNAs, and their interactions underlying macrophage aging and response to cholesterol through bioinformatical analysis in order to get a better understanding of the mechanism of AMD. Methods The microarray data were obtained from Gene Expression Omnibus (accession GSE111304 and GSE111382). The age-related differentially expressed genes in macrophages were identified using R software. Further miRNA-mRNA interactions were analyzed through miRWalk, mirTarBase, starBase, and then produced by Cytoscape. The functional annotations including Gene Ontology and KEGG pathways of the miRNA target genes were performed by the DAVID and the STRING database. In addition, protein-protein interaction network was constructed to identify the key genes in response to exogenous cholesterol. Results When comparing aged and young macrophages, a total of 14 miRNAs and 101 mRNAs were detected as differentially expressed. Besides, 19 validated and 544 predicted miRNA-mRNA interactions were detected. Lipid metabolic process was found to be associated with macrophage aging through functional annotations of the miRNA targets. After being treated with oxidized and acetylated low-density lipoprotein, miR-714 and 16 mRNAs differentially expressed in response to both kinds of cholesterol between aged and young macrophages. Among them, 6 miRNA-mRNA predicted pairs were detected. The functional annotations were mainly related to lipid metabolism process and farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified to be the key gene in the difference of response to cholesterol between aged and young macrophages. Conclusions Lipid metabolic process was critical in both macrophage aging and response to cholesterol thus was regarded to be associated with the occurrence and progression of AMD. Moreover, miR-714-FDFT1 may modulate cholesterol homeostasis in aged macrophages and have the potential to be a novel therapeutic target for AMD.