ceRNA network construction and identification of hub genes as novel therapeutic targets for age-related cataracts using bioinformatics

Abstract

Background The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC). Methods We obtained the transcriptome datafile of th ree ARC samples and three healthy, age-matched samples and used differential expression analyses to identify the differentially expressed genes (DEGs). The differential lncRNA-associated competing endogenous (ceRNA) network, and the protein-protein network (PPI) were constructed using Cytoscape and STRING. Cluster analyses were performed to identify the underlying molecular mechanisms of the hub genes affecting ARC progression. To verify the immune status of the ARC patients, immune-associated analyses were also conducted. Results The PPI network identified the FOXO1 gene as the hub gene with the highest score, as calculated by the Maximal Clique Centrality (MCC) algorithm. The ceRNA network identified lncRNAs H19, XIST, TTTY14, and MEG3 and hub genes FOXO1, NOTCH3, CDK6, SPRY2, and CA2 as playing key roles in regulating the pathogenesis of ARC. Additionally, the identified hub genes showed no significant correlation with an immune response but were highly correlated with cell metabolism, including cysteine, methionine, and galactose. Discussion The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.

A role for YAP/FOXM1/Nrf2 axis in oxidative stress and apoptosis of cataract induced by UVB irradiation

“…The methods employed for the collection of clinical samples (including normal group and ARC patients) and transcriptome data (GSE213546) were documented in our prior study 30 . Through bioinformatic analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed significant enrichment of the Hippo pathway (Figure S1) and subsequent downregulation of downstream genes associated with YAP, such as CyclinD1 (CCND1), Connective tissue growth factor (CTGF), Smad7, inhibitor of DNA binding (Id) 1, Id2, and axis inhibition protein 2 (Axin2), which are known to be involved in anti‐apoptotic processes (Table S1).…”