Research Paper Volume 16, Issue 6 pp 5435—5451
Identification of key lncRNAs in age-related macular degeneration through integrated bioinformatics and experimental validation
- 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou 510060, China
Received: October 10, 2023 Accepted: February 7, 2024 Published: March 14, 2024
https://doi.org/10.18632/aging.205656How to Cite
Copyright: © 2024 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
This study aimed to identify key long noncoding RNAs (lncRNAs) in age-related macular degeneration (AMD) patients and to identify relevant pathological mechanisms of AMD development. We identified 407 differentially expressed mRNAs and 429 differentially expressed lncRNAs in retinal pigment epithelium (RPE) and retina in the macular region of AMD patients versus controls (P < 0.05 and |log2FC| > 0.585) from GSE135092. A total of 14 key differentially expressed mRNAs were obtained through external data validation from GSE115828. A miRNA-mRNA and miRNA-lncRNA network containing 52 lncRNA nodes, 49 miRNA nodes, 14 mRNA nodes and 351 edges was constructed via integrated analysis of these components. Finally, the LINC00276-miR-619-5p-IFIT3 axis was identified via protein-protein network analysis. In the t-BH-induced ARPE-19 senescent cell model, LINC00276 and IFIT3 were downregulated. Overexpression of LINC00276 could accelerate cell migration in combination with IFIT3 upregulation. This compelling finding suggests that LINC00276 plays an influential role in the progression of AMD, potentially through modulating senescence processes, thereby setting a foundation for future investigative efforts to verify this relationship.
Abbreviations
AMD: age-related macular degeneration; RPE: retinal pigment epithelium; lncRNA: long noncoding RNA; IFIT3: interferon-induced protein with tetratricopeptide repeats 3; DEG: differentially expressed genes; GEO: Gene expression omnibus; DAVID: Database for Annotation, Visualization, and Integrated Discovery; PPI: protein-protein interaction; STRING: Search Tool for the Retrieval of Interacting Genes/Proteins; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological processes; ceRNA: competing endogenous RNA; miRNA: microRNA.