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Identification of the aberrantly methylated differentially expressed genes in proliferative diabetic retinopathy.
Experimental Eye Research ( IF 3.4 ) Pub Date : 2020-07-25 , DOI: 10.1016/j.exer.2020.108141
Aiwen Miao 1 , Jing Lu 1 , Yishen Wang 1 , Shudi Mao 1 , Yamei Cui 1 , Jianying Pan 1 , Lisha Li 1 , Yan Luo 1
Affiliation  

Diabetic retinopathy (DR) is the most common complication of diabetes. Proliferative DR (PDR) is a more advanced stage of DR, which can cause severe impaired vision and even blindness. However, the precise pathological mechanisms of PDR remain unknown. DNA methylation serves an important role in the initiation and progression of numerous types of disease including PDR. The purpose of this study was to identify the aberrantly methylated differentially expressed genes (DEGs) as potential therapeutic targets of PDR. The gene expression microarray dataset GSE60436 and the methylation profiling microarray dataset GSE57362 were used to determine the aberrantly methylated DEGs in PDR, utilizing normal retinas as controls and fibrovascular membranes (FVMs) in patients with PDR as PDR samples. The functional term and signaling pathway enrichment analysis of the selected genes were subsequently performed. In addition, protein-protein interaction (PPI) networks were constructed to determine the hub genes, and the network of transcriptional factor (TF) and target hub genes was also analyzed. In total, 132 hypomethylated genes were found to be upregulated, whereas 172 hypermethylated genes were discovered to be downregulated in PDR. The hypomethylated upregulated genes were found to be enriched in the pathways, such as “cell-substrate adhesion”, “adherens junction”, “cell adhesion molecule binding” and “extracellular matrix receptor interactions”. Meanwhile, the hypermethylated downregulated genes were enriched in the pathways, such as “visual perception”, “presynapse” and the “synaptic vesicle cycle”. Based on the PPI analysis, a total of eight hub genes were identified: CTGF, SERPINH1, LOX, RBP3, OTX2, RPE65, OPN1SW and NRL. It was hypothesized that the aberrant methylation of these genes might be related to the possible pathophysiology of PDR. An important transcriptional factor, TFDP1, was discovered to share the closest interactions with the hub genes from the gene-TF network. In conclusion, the present study identified an association among DNA methylation and gene expression in PDR using bioinformatics analysis, and identified the hub genes which might be potential methylation-based diagnosis and treatment targets for PDR in the near future.



中文翻译:

增生性糖尿病性视网膜病变中异常甲基化差异表达基因的鉴定。

糖尿病性视网膜病(DR)是糖尿病最常见的并发症。增殖性DR(PDR)是DR的晚期,可导致严重的视力受损甚至失明。但是,PDR的确切病理机制仍然未知。DNA甲基化在包括PDR在内的多种疾病的发生和发展中起着重要作用。这项研究的目的是确定异常甲基化的差异表达基因(DEG)作为PDR的潜在治疗靶标。将基因表达微阵列数据集GSE60436和甲基化分析微阵列数据集GSE57362用于确定PDR中异常甲基化的DEG,以正常视网膜作为对照,并以PDR患者的纤维血管膜(FVM)作为PDR样品。随后进行所选基因的功能术语和信号传导途径富集分析。另外,构建蛋白质-蛋白质相互作用(PPI)网络来确定轮毂基因,并且还分析了转录因子(TF)和目标轮毂基因的网络。总共发现132个低甲基化基因被上调,而172个高甲基化基因被发现在PDR中被下调。发现低甲基化的上调基因在诸如“细胞-底物粘附”,“粘附分子连接”,“细胞粘附分子结合”和“细胞外基质受体相互作用”的途径中富集。同时,高甲基化的下调基因在“视觉感知”,“突触前”和“突触小泡循环”等途径中富集。根据PPI分析,CTGFSERPINH1LOXRBP3OTX2RPE65OPN1SWNRL。假设这些基因的异常甲基化可能与PDR的可能病理生理有关。发现重要的转录因子TFDP1与来自基因-TF网络的中枢基因共享最紧密的相互作用。总之,本研究使用生物信息学分析确定了PDR中DNA甲基化与基因表达之间的关联,并确定了可能在不久的将来可能成为基于PLP甲基化的诊断和治疗目标的中心基因。

更新日期:2020-09-02
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