Decoding the ceRNA network in diabetic retinopathy: Identification of MEG3 as a hub lncRNA and therapeutic target

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus that primarily affects individuals aged 20–65 years and accounts for 2.6% of global vision loss. Often asymptomatic or presenting only minor visual disturbances in its early stages, DR can progress to severe blindness, underscoring the need for novel drug targets. This study aimed to identify potential long noncoding RNA (lncRNA) drug targets and construct a competing endogenous RNA (ceRNA) network (lncRNA–miRNA–mRNA) associated with DR using integrative computational biology approaches. Differential expression analysis was performed on lncRNAs and mRNAs from highly glycosylated ARPE-19 cells and miRNAs from proliferative DR (PDR) patients obtained from the GEO database. Leveraging the ceRNA hypothesis, we constructed a lncRNA–miRNA–mRNA network and identified hub lncRNAs through topological analysis and gene set analysis (GSA). Our findings revealed 572 differentially expressed mRNAs (DEGs), 87 miRNAs (DEMs), and 244 lncRNAs (DELs) linked to DR. The resulting ceRNA network consisted of 59 DELs, 240 DEGs, and 66 DEMs interconnected through 344 nodes and 573 edges, with MEG3 and OLMALINC emerging as key hub lncRNAs. GSA of MEG3- and OLMALINC-associated mRNAs revealed important biological processes and pathways responsible for the pathogenesis of DR. Validation of lncRNAs was performed using human samples from the GSE60436 dataset, which revealed that the binding affinity of MEG3, a hub lncRNA in the ceRNA network, was greater for the FDA-approved drug gentamicin than for the other drugs, as the binding site of the former for MEG3 was greater for the former than for the latter for the latter, suggesting a potential mechanism for enhancing its expression. Overall, our results from this study provide novel insights into ceRNA-mediated regulation in DR and suggest that MEG3 may serve as a promising hub lncRNA for the prevention of DR, warranting further experimental validation.