Age-related lncRNA alterations of SDHAP2_miR-17-5p/miR-20b-5p_RAB11FIP1 ceRNA network in donor-derived human limbal...

Limbal epithelial cells (LECs) play a crucial role in preserving ocular surface stability and ensuring the normal function of the corneal epithelium. The functional capacity of LECs diminishes with age, playing a part in the onset of ocular diseases linked to aging. Although long non-coding RNAs (lncRNAs) are key regulators of gene expression and are known to be involved in numerous ocular pathologies, their expression dynamics during aging in LECs are not yet well characterized.

High-throughput RNA sequencing and computational analysis were utilized to characterize age-related differences in mRNA and lncRNA in human LECs derived from young and old donors. 90 lncRNAs and 177 mRNAs with significant age-associated expression changes were identified. Functional enrichment was assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A competing endogenous RNA (ceRNA) network was constructed using Cytoscape and cytoHubba, focusing on the interaction between lncRNAs, miRNAs and mRNAs.

The study identified the potential ceRNA network, SDHAP2_miR-17-5p/miR-20b-5p_RAB11FIP1, that might be crucial in age-related changes of the LECs. Quantitative RT-PCR validated the expression for SDHAP2 (downregulated), miR-17-5p (upregulated), miR-20b-5p (upregulated), and RAB11FIP1 (downregulated) in the old group, consistent with transcriptome data. Functional analysis suggested this network may be involved in oxidative stress responses and cellular senescence.

Our findings reveal age-associated lncRNA and mRNA expression alterations in human LECs and highlight the SDHAP2_miR-17-5p/miR-20b-5p_RAB11FIP1 ceRNA network as a potential molecular indicator and therapeutic entry point for age-related ocular surface diseases.