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image of Identification of the Role of Necroptosis-Related Genes in the Oxidative Damage of Lens Epithelial Cells and Validation in Ultraviolet B-induced Cataract in Rats

Abstract

Introduction

The specific role of necroptosis in the pathogenesis of cataracts remains unclear. This study aimed to identify and validate the genes related to necroptosis in the development of cataracts through bioinformatics analysis.

Method

We utilized RNA sequencing data (GSE161701) from the Gene Expression Omnibus (GEO) database and employed R software to perform differential expression analysis of necroptosis-related genes (NRGs) in lens epithelial cells (LECs) under oxidative stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to evaluate the functions of necroptosis-related differentially expressed genes (NRDEGs) and their associated pathways. Additionally, a diagnostic model was established using LASSO regression to select hub genes, and protein-protein interaction (PPI) networks, mRNA-miRNA, and mRNA-drug regulatory networks were constructed. Immune infiltration analysis was performed using the xCell and CIBERSORT algorithms, and the differential expression of hub genes was validated in a UVB-induced rat cataract model using RT-qPCR and immunohistochemistry.

Results

The results indicated that oxidative stress promoted necroptosis in LECs, involving 86 NRDEGs and nine hub genes. GO and KEGG analyses revealed significant enrichment in necroptosis-associated pathways. Furthermore, we identified 58 mRNA-miRNA interactions and 131 potential molecular compounds or drugs. The immune infiltration analysis showed that certain immune cells exhibited significantly elevated expression in the cataract group, with notable correlations between some immune cells and hub genes. RT-qPCR and immunohistochemistry confirmed the expression of 9 hub genes and 3 key necroptosis genes. BAX, CXCL1, EPAS1, JUN, LRP1, RBM14, SERTAD1, and TNFAIP3 were highlighted as potential diagnostic and therapeutic targets.

Conclusion

This study identified key NRDEGs involved in the pathogenesis of cataracts under oxidative stress through bioinformatics analyses, potentially providing new targets and research directions for future cataract prevention and treatment.

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2025-04-17
2025-10-31

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Identification of the Role of Necroptosis-Related Genes in the Oxidative Damage of Lens Epithelial Cells and Validation in Ultraviolet B-induced Cataract in Rats
Bentham Science Publishers ; https://doi.org/10.2174/0113862073365864250312043532
/content/journals/cchts/10.2174/0113862073365864250312043532
/content/journals/cchts/10.2174/0113862073365864250312043532
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Supplementary Fig. . Normalization of GSE161701 dataset. Supplementary Fig. . KEGG enrichment pathway map. Supplementary Fig. . ROC curves and AUC of the nine hub genes. Supplementary Table . Cataract dataset information list. Supplementary Table . Necroptosis-related differentially expressed genes. Supplementary Table 3. GO enrichment analysis results of NRDEGs. Supplementary Table . KEGG enrichment analysis results of NRDEGs. Supplementary Table . GSEA analysis of the GSE161701 dataset. Supplementary Table . GSVA analysis of the GSE161701 dataset. Supplementary Table . mRNA-miRNA interaction network nodes. Supplementary Table . mRNA-drug interaction network nodes.

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  • Article Type:     Research Article
Keywords: cataract ; oxidative damage ; programmed cell death ; lens epithelial cells ; necroptosis-related genes ; GEO ; Necroptosis ; LASSO regression

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