ArticleBMC ophthalmology2026
Correlation between the expression levels of miR-199a-3p and FN1 in serum and aqueous humor and the severity of type 2 diabetic retinopathy in a Chinese population.
Article in BMC ophthalmology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTo investigate the correlation between the expression levels of microRNA-199a-3p (miR-199a-3p) and Fibronectin 1 (FN1) in serum and aqueous humor and the severity of Type 2 Diabetic Retinopathy (DR) in a Chinese population.
methodsThe dataset GSE102485 (containing 3 normal controls and 22 DR samples) was downloaded from the Gene Expression Omnibus (GEO) database as a discovery set, and the dataset GSE60436 (containing 3 normal controls and 6 DR samples) was used as a validation set. The limma package was employed for differential expression analysis to identify differentially expressed genes (DEGs). The potential downstream target genes of miR-199a-3p were predicted using seven databases including ENCORI. A Venn diagram was used to identify the intersection between the DEGs and the predicted miR-199a-3p target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the intersecting genes. A protein-protein interaction (PPI) network was constructed, and the CIBERSORT algorithm was applied for in-depth analysis of FN1 expression characteristics. Furthermore, the expression pattern of FN1 was validated in independent datasets concerning its association with miR-199a-3p and DR. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to verify the relationship between the expression levels of miR-199a-3p and FN1 in clinical serum and aqueous humor samples and DR severity.
resultsBioinformatics analysis identified a total of 458 DEGs, comprising 214 upregulated and 244 downregulated genes. A heatmap was generated for the top 50 most significantly altered genes. Venn diagram analysis revealed three overlapping genes (PHYHIPL, FN1, CALD1) between the DEGs from GSE102485 and the predicted miR-199a-3p target genes. Further analysis using the miRDB website indicated that FN1 had the strongest correlation with miR-199a-3p, suggesting both as potential important biomarkers for DR. Additionally, the relative expression level of serum miR-199a-3p was significantly negatively correlated with fasting plasma glucose (FPG) (r = -0.425, P = 0.012), glycated hemoglobin (HbA1c) (r = -0.513, P = 0.003), and duration of diabetes (r = -0.587, P < 0.001), indicating its decrease with elevated blood glucose and prolonged disease course. Conversely, serum FN1 levels showed significant positive correlations with FPG (r = 0.458, P = 0.008), HbA1c (r = 0.621, P < 0.001), and diabetes duration (r = 0.694, P < 0.001), suggesting that poor glycemic control and disease progression may promote FN1 overexpression. Both biomarkers demonstrated good diagnostic value for DR, with miR-199a-3p exhibiting the highest diagnostic efficacy.
conclusionThe expression levels of miR-199a-3p and FN1 in serum and aqueous humor are significantly correlated with the severity of Type 2 Diabetic Retinopathy, highlighting their potential as non-invasive diagnostic and prognostic biomarkers for DR.
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