Bioinformatical Analysis of miRNA‐mRNA Interaction Network Underlying Macrophage Aging and Cholesterol‐Responsive Difference between Young and Aged Macrophages

Abstract

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.

Non-Coding RNAs: Novel Regulators of Macrophage Homeostasis in Ocular Vascular Diseases

“…Recent studies have tried to identify ncRNAs that regulate macrophage homeostasis in AMD. One study showed the roles of macrophage senescence and cholesterol homeostasis in AMD, advocating that an miR-714- FDFT1 network may steer the development of AMD by regulating cholesterol homeostasis in aging macrophages [ 72 ]. Another study explored the effects of miRNAs on the neovascularization and inflammatory response in AMD.…”

Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

“…Extensive genomic studies have verified that abnormal expressions of multiple mRNAs of genes involved in LUAD tumorigenesis and progression play vital roles ( Herbst et al, 2018 ). The miRNA–mRNA regulatory network is characterized in such a way that individual miRNA could regulate a wealth of different mRNAs of genes, and the individual mRNA of a target gene could be correspondingly suppressed by multiple different miRNAs ( Cui et al, 2020 ; Li et al, 2020 ; Liu et al, 2020 ). Thus, it is necessary to examine the miRNA–mRNA regulatory network in LUAD to advance our understanding of its molecular mechanisms.…”