{"title":"坏死相关基因在晶状体上皮细胞氧化损伤中的作用及其在紫外线b诱导大鼠白内障中的验证。","authors":"Yongshun Liang, Qingqiao Gan, Xin Zhong, Tian Lan, Yingqin Yang, Hao Liang","doi":"10.2174/0113862073365864250312043532","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Method: </strong>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 mRNAdrug 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Yongshun Liang, Qingqiao Gan, Xin Zhong, Tian Lan, Yingqin Yang, Hao Liang\",\"doi\":\"10.2174/0113862073365864250312043532\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The specific role of necroptosis in the pathogenesis of cataracts remains unclear. 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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.</p><p><strong>Results: </strong>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. 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引用次数: 0
摘要
导读：坏死性上睑下垂在白内障发病中的具体作用尚不清楚。本研究旨在通过生物信息学分析，鉴定和验证白内障发生过程中与坏死性下垂相关的基因。方法：利用Gene Expression Omnibus （GEO）数据库中的RNA测序数据（GSE161701），利用R软件对氧化应激条件下晶状体上皮细胞（LECs）中坏死坏死相关基因（NRGs）的差异表达进行分析。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）分析来评估坏死相关差异表达基因（NRDEGs）及其相关途径的功能。此外，利用LASSO回归建立诊断模型，筛选中心基因，构建蛋白-蛋白相互作用（PPI）网络、mRNA-miRNA、mRNAdrug调控网络。采用xCell和CIBERSORT算法进行免疫浸润分析，并采用RT-qPCR和免疫组织化学方法在uvb诱导的大鼠白内障模型中验证hub基因的差异表达。结果：氧化应激促进LECs坏死性坏死，涉及86个NRDEGs和9个hub基因。GO和KEGG分析显示坏死下垂相关通路显著富集。此外，我们鉴定了58种mRNA-miRNA相互作用和131种潜在的分子化合物或药物。免疫浸润分析显示，部分免疫细胞在白内障组表达显著升高，部分免疫细胞与中枢基因有显著相关性。RT-qPCR和免疫组化证实了9个中枢基因和3个坏死性下垂关键基因的表达。BAX、CXCL1、EPAS1、JUN、LRP1、RBM14、SERTAD1和TNFAIP3被强调为潜在的诊断和治疗靶点。结论：本研究通过生物信息学分析，确定了氧化应激下白内障发病机制的关键NRDEGs，为今后白内障防治提供了新的靶点和研究方向。
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.
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 mRNAdrug 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.
期刊介绍：
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.
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