Comprehensive bioinformatics analysis of metabolism‑related microRNAs in high myopia in young and old adults with age‑related cataracts.

Abstract

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.