Huang Fanfan, Chen Yanyi, Wu Jiaxue, Zheng Shijie, Huang Rongxi, Wan Wenjuan, Hu Ke
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Centre for Ocular Diseases, Chongqing 400016, P.R. China.
Department of Endocrinology, Chongqing General Hospital, Chongqing 401147, P.R. China.
Mol Med Rep. 2025 Feb;31(2). doi: 10.3892/mmr.2024.13411. Epub 2024 Dec 5.
High myopia and age‑related cataracts are prevalent ocular disorders that compromise visual acuity. The molecular mechanisms underlying these conditions remain largely unclear. Here, microRNA (miRNA or miR) sequencing was performed on aqueous humor samples obtained from individuals with age‑related cataracts and high myopia (AH, n=9), young patients with high myopia (YH, n=9) and a control group of elderly patients with age‑related cataracts, matched in terms of sex and age (AN, n=9). miRNA sequencing and differential expression were performed. Intersecting miRNAs were identified, as well as metabolism‑related genes from MsigDB were intersected with miRNA target genes. Functional enrichment was performed and disease targets predicted using DisGeNET. A protein‑protein interaction network was built with STRING, and hub genes were identified via Cytoscape. GeneMANIA analyzed hub genes, while drug predictions were made using Comparative Toxicogenomics Database. Long non‑coding RNAs and transcription factors were predicted via mirNet and ChEA3. Results were validated by RT‑qPCR. A total of 18 miRNAs were significantly differential expressed between AH and AN group, of which eight were up‑ and 10 were downregulated. A total of 23 miRNAs were significantly differential expressed between the YH and AN group, of which six were up‑ and 17 were downregulated. hsa‑miR‑490‑3p, hsa‑miR‑4423‑3p and hsa‑miR‑4485‑3p may serve as characteristic miRNAs. A total of 289 target genes were predicted. Functional enrichment analysis yielded 169 terms, with 'herpes simplex virus 1 infection' the most significantly enriched. There were 19 metabolism‑associated target genes linked with these miRNAs, suggesting a potential role of metabolic processes in pathogenesis of these conditions. The biosynthetic process of carbohydrate derivatives may serve a key role during the development of high myopia. There were 10 hub genes and Propionyl‑CoA Carboxylase Subunit β could potentially serve as a biomarker. Drugs that could modulate their function were predicted; cyclosporine, tretinoin and acetaminophen may exert a broad influence on these hub genes. Hub gene networks based on the miRNAs were constructed to predict 44 associated long non‑coding RNAs and 98 transcription factors. The present findings offer novel insights into the molecular mechanisms of age‑related cataracts and high myopia and propose potential therapeutic targets.
高度近视和年龄相关性白内障是常见的损害视力的眼部疾病。这些病症背后的分子机制在很大程度上仍不清楚。在此，对从年龄相关性白内障和高度近视患者（AH，n = 9）、年轻高度近视患者（YH，n = 9）以及年龄和性别匹配的年龄相关性白内障老年患者对照组（AN，n = 9）获得的房水样本进行了微小RNA（miRNA或miR）测序。进行了miRNA测序和差异表达分析。鉴定了相交的miRNA，并将来自MsigDB的代谢相关基因与miRNA靶基因进行了交叉分析。使用DisGeNET进行功能富集并预测疾病靶点。用STRING构建蛋白质-蛋白质相互作用网络，并通过Cytoscape鉴定枢纽基因。用GeneMANIA分析枢纽基因，同时使用比较毒理基因组学数据库进行药物预测。通过mirNet和ChEA3预测长链非编码RNA和转录因子。结果通过RT-qPCR验证。AH组和AN组之间共有18种miRNA显著差异表达，其中8种上调，10种下调。YH组和AN组之间共有23种miRNA显著差异表达，其中6种上调，17种下调。hsa-miR-490-3p、hsa-miR-4423-3p和hsa-miR-4485-3p可能作为特征性miRNA。共预测了289个靶基因。功能富集分析产生了169个条目，其中“单纯疱疹病毒1感染”富集最为显著。有19个与代谢相关的靶基因与这些miRNA相关联，表明代谢过程在这些病症的发病机制中可能起作用。碳水化合物衍生物的生物合成过程可能在高度近视的发展过程中起关键作用。有10个枢纽基因，丙酰辅酶A羧化酶亚基β可能作为生物标志物。预测了可调节其功能的药物；环孢素、维甲酸和对乙酰氨基酚可能对这些枢纽基因产生广泛影响。基于这些miRNA构建了枢纽基因网络，以预测44个相关的长链非编码RNA和98个转录因子。本研究结果为年龄相关性白内障和高度近视的分子机制提供了新的见解，并提出了潜在的治疗靶点。
