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构建与年龄相关性黄斑变性相关的铁死亡相关环状 RNA-miRNA-mRNA 网络。

Construction of a ferroptosis-associated circRNA-miRNA-mRNA network in age-related macular degeneration.

机构信息

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai, China.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.

出版信息

Exp Eye Res. 2022 Nov;224:109234. doi: 10.1016/j.exer.2022.109234. Epub 2022 Aug 28.

Abstract

Age-related macular degeneration (AMD) is a leading cause of severe vision impairment in the aging population. However, the underlying molecular mechanism remains unclear. Ferroptosis is a novel non-apoptotic programmed cell death pathway, that contributes to AMD. In addition, non-coding RNA-led epigenetic profile was identified in the regulation of AMD progression. Considering that non-coding RNAs are vital regulators of ferroptosis-related genes in various pathological events, we explored and constructed a ferroptosis-associated circRNA-miRNA-mRNA network in AMD. Differential expression of fourteen ferroptosis-associated genes were identified based on our microarray analysis and the FerrDb tool at the threshold of P < 0.05 and log|fold change| ≥ 1, which were subsequently validated by the public datasets. We further screened eight miRNAs via public datasets and the miRNet database. Based on these eight miRNAs, 23 circRNAs were mined using the Starbase tool. Taking all these together, we obtained a ferroptosis-related network with 414 pairs of circRNA-miRNA-mRNA, which are potential targets in future AMD treatments.

摘要

年龄相关性黄斑变性(AMD)是导致老年人群视力严重受损的主要原因。然而,其潜在的分子机制尚不清楚。铁死亡是一种新的非细胞凋亡程序性细胞死亡途径,与 AMD 有关。此外,在 AMD 进展的调控中发现了非编码 RNA 主导的表观遗传特征。鉴于非编码 RNA 在各种病理事件中铁死亡相关基因的调控中是至关重要的,我们探索并构建了 AMD 中的铁死亡相关 circRNA-miRNA-mRNA 网络。基于我们的微阵列分析和 FerrDb 工具,在 P < 0.05 和 log|fold change| ≥ 1 的阈值下,鉴定了 14 个铁死亡相关基因的差异表达,随后通过公共数据集进行了验证。我们进一步通过公共数据集和 miRNet 数据库筛选了 8 个 miRNAs。基于这 8 个 miRNAs,使用 Starbase 工具挖掘了 23 个 circRNAs。综上所述,我们获得了一个包含 414 对 circRNA-miRNA-mRNA 的铁死亡相关网络,这些可能是未来 AMD 治疗的潜在靶点。

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