Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
PeerJ. 2023 Mar 23;11:e15054. doi: 10.7717/peerj.15054. eCollection 2023.
The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC).
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.
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.
The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.
本研究旨在探讨与年龄相关性白内障（ARC）发病机制相关的遗传和表观遗传机制。
我们获得了三个 ARC 样本和三个年龄匹配的健康样本的转录组数据文件，并使用差异表达分析来识别差异表达基因（DEGs）。使用 Cytoscape 和 STRING 构建差异 lncRNA 相关竞争内源性（ceRNA）网络和蛋白质-蛋白质网络（PPI）。通过聚类分析来识别影响 ARC 进展的关键基因的潜在分子机制。为了验证 ARC 患者的免疫状态，还进行了免疫相关分析。
PPI 网络确定 FOXO1 基因为关键基因，其得分由最大团中心度（MCC）算法计算得出。ceRNA 网络确定了 lncRNAs H19、XIST、TTTY14 和 MEG3 以及关键基因 FOXO1、NOTCH3、CDK6、SPRY2 和 CA2 在调节 ARC 发病机制中发挥关键作用。此外，鉴定的关键基因与免疫反应没有显著相关性，但与细胞代谢高度相关，包括半胱氨酸、蛋氨酸和半乳糖。
本研究的结果可能为 ARC 发病机制提供线索，并可能对未来的治疗研究具有重要意义。
