Bioinformatical Analysis of miRNA-mRNA Interaction Network Underlying Macrophage Aging and Cholesterol-Responsive
Jianqing Li1, Xue Yin1, Bingyu Zhang1
1Department of Ophthalmology, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
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.
Insights
Macrophage aging, linked to age-related macular degeneration (AMD), involves altered lipid metabolism. MiR-714 and FDFT1 may regulate cholesterol in aged macrophages, offering a potential new therapeutic target for AMD.
Area of Science:
- Molecular Biology
- Genomics
- Ophthalmology
Background:
- Macrophage aging is implicated in age-related macular degeneration (AMD) pathogenesis.
- Understanding the molecular mechanisms of macrophage aging and cholesterol response is crucial for AMD research.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) and messenger RNAs (mRNAs) involved in macrophage aging.
- To elucidate miRNA-mRNA interactions influencing macrophage response to cholesterol.
- To gain insights into the mechanisms underlying AMD.
Main Methods:
- Bioinformatic analysis of microarray data (GSE111304, GSE111382) using R software.
- Identification of differentially expressed genes and miRNA-mRNA interactions via miRWalk, mirTarBase, and starBase.
- Functional annotation (Gene Ontology, KEGG) and protein-protein interaction network construction using DAVID, STRING, and Cytoscape.
Main Results:
- 14 miRNAs and 101 mRNAs were differentially expressed in aged versus young macrophages.
- Lipid metabolic processes were significantly associated with macrophage aging.
- miR-714 and 16 mRNAs showed differential expression in response to cholesterol, with FDFT1 identified as a key gene.
Conclusions:
- Lipid metabolism is critical in macrophage aging and cholesterol response, linking it to AMD occurrence and progression.
- The miR-714-FDFT1 axis may modulate cholesterol homeostasis in aged macrophages.
- This axis presents a potential novel therapeutic target for AMD.
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