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.
Aging (Albany NY). 2024 Mar 14;16(6):5435-5451. doi: 10.18632/aging.205656.
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.
本研究旨在鉴定与年龄相关性黄斑变性(AMD)患者相关的关键长非编码 RNA(lncRNA),并鉴定 AMD 发展的相关病理机制。我们从 GSE135092 中鉴定了 AMD 患者与对照组相比,在视网膜色素上皮(RPE)和黄斑区视网膜中差异表达的 407 个 mRNAs 和 429 个 lncRNAs(P<0.05,|log2FC|>0.585)。通过从 GSE115828 中进行外部数据验证,共获得了 14 个关键差异表达的 mRNAs。通过对这些成分的综合分析,构建了包含 52 个 lncRNA 节点、49 个 miRNA 节点、14 个 mRNA 节点和 351 个边缘的 miRNA-mRNA 和 miRNA-lncRNA 网络。最后,通过蛋白质-蛋白质网络分析鉴定了 LINC00276-miR-619-5p-IFIT3 轴。在 t-BH 诱导的 ARPE-19 衰老细胞模型中,LINC00276 和 IFIT3 下调。LINC00276 的过表达可与 IFIT3 的上调协同促进细胞迁移。这一引人注目的发现表明,LINC00276 在 AMD 的进展中发挥着重要作用,可能通过调节衰老过程来实现,从而为未来验证这种关系的研究奠定了基础。