性别特异性 lncRNA-miRNA-mRNA 调控网络揭示原发性开角型青光眼的潜在基因

Gender-specific lncRNA-miRNA-mRNA regulatory network to reveal potential genes for primary open-angle glaucoma.

机构信息

Department of Ophthalmology, General Hospital of Southern Theatre Command of PLA, No.111, Liuhua Road, Guangzhou City, Guangdong Province, 510010, China.

出版信息

Exp Eye Res. 2023 Nov;236:109668. doi: 10.1016/j.exer.2023.109668. Epub 2023 Sep 27.

DOI:10.1016/j.exer.2023.109668

PMID:37774963

Abstract

BACKGROUND

Investigation of biomarkers may facilitate understanding the mechanisms of primary open-angle glaucoma (POAG) and developing therapeutic targets. This study aimed to identify potential genes based on competing endogenous RNA (ceRNA) network for POAG.

METHODS

Based on long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) from the Gene Expression Omnibus (GEO) database, we identified differential expressed lncRNAs (DELs), differential expressed miRNAs (DEMis) and differential expressed mRNAs (DEMs) and then constructed a ceRNA network. Through weighted gene co-expression network analysis (WGCNA), we identified gender-specific genes for gender-associated ceRNA network construction, followed by the protein-protein interaction (PPI) network and functional enrichment analysis to screen hub genes and reveal their functions. The expression levels of hub genes were measured in steroid-induced ocular hypertension (SIOH) mice.

RESULTS

A total of 175 DELs, 727 DEMs and 45 DEMis were screened between control and POAG samples. Seven modules were identified through WGCNA and one module was associated with gender of POAG patients. We discovered 41 gender-specific genes for gender-associated ceRNA construction and then identified 8 genes (NAV3, C1QB, RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1), which were enriched in cell cycle-related pathways and immune-related pathways. C1QB, RXRB, Top1 and ZNF207 were highly interacted with other proteins. The expression levels of NAV3 and C1QB were downregulated in SIOH, while the levels of RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1 were upregulated in SIOH.

CONCLUSION

This study identifies hub genes associated with the pathogenesis of gender-specific POAG and provides potential biomarkers for POAG.

摘要

背景

生物标志物的研究可能有助于理解原发性开角型青光眼（POAG）的发病机制并为治疗靶点的开发提供依据。本研究旨在基于竞争内源性 RNA（ceRNA）网络鉴定 POAG 的潜在基因。

方法

基于基因表达综合数据库（GEO）中的长链非编码 RNA（lncRNA）、微小 RNA（miRNA）和信使 RNA（mRNA），我们鉴定了差异表达的 lncRNA（DEL）、差异表达的 miRNA（DEMi）和差异表达的 mRNA（DEM），然后构建了 ceRNA 网络。通过加权基因共表达网络分析（WGCNA），我们鉴定了性别相关 ceRNA 网络构建的性别特异性基因，随后进行蛋白质-蛋白质相互作用（PPI）网络和功能富集分析，筛选枢纽基因并揭示其功能。在类固醇诱导的眼内压升高（SIOH）小鼠中测量了枢纽基因的表达水平。

结果

在对照和 POAG 样本之间筛选出 175 个 DEL、727 个 DEM 和 45 个 DEMi。通过 WGCNA 鉴定出 7 个模块，其中一个模块与 POAG 患者的性别相关。我们发现 41 个性别特异性基因用于性别相关的 ceRNA 构建，然后鉴定出 8 个基因（NAV3、C1QB、RXRB、P2RY4、ADAM15、VAV3、ZNF207 和 TOP1），这些基因富集在细胞周期相关通路和免疫相关通路中。C1QB、RXRB、Top1 和 ZNF207 与其他蛋白质高度相互作用。在 SIOH 中，NAV3 和 C1QB 的表达水平下调，而 RXRB、P2RY4、ADAM15、VAV3、ZNF207 和 TOP1 的表达水平上调。