构建 miRNA-mRNA 调控网络表明原发性开角型青光眼的潜在生物标志物。

Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma.

机构信息

Aier Glaucoma Institute, Changsha Aier Eye Hospital, Changsha, Hunan Province, China.

The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

出版信息

BMC Med Genomics. 2023 Nov 8;16(1):280. doi: 10.1186/s12920-023-01698-2.

DOI:10.1186/s12920-023-01698-2

PMID:37940950

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10634160/

Abstract

BACKGROUND

Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary open‑angle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG.

METHODS

miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis.

RESULTS

A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways.

CONCLUSION

In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG.

摘要

背景

研究表明，小梁网（TM）功能障碍导致的眼内压升高是原发性开角型青光眼（POAG）不可逆视神经损伤的主要危险因素。越来越多的证据表明，microRNA（miRNA）在 POAG 的发病机制中起着至关重要的作用。本研究旨在构建 miRNA-mRNA 调控网络，并寻找 POAG 的生物标志物。

方法

通过微阵列分析评估了对照组和 POAG 患者 TM 样本中的 miRNA 和 mRNA 表达谱。通过 miEAA 和 miRNet 预测差异表达 miRNA（DEmiRNA）的靶基因。然后对差异表达 mRNA（DEmRNA）进行 GO 和 KEGG 通路分析。通过 STRING 数据库和 Cytoscape 软件识别 top 30 个 hub 基因的 PPI，并建立 miRNA-mRNA 网络。使用 GSE27276 和 GSE105269 数据集分别验证 hub 基因在 TM 和房水中的表达，并预测用于 POAG 的潜在生物标志物。最后，进行 GSEA 分析以评估 POAG 发病机制的主要信号通路。

结果

与对照组相比，POAG 的 TM 中发现 29 个上调和 7 个下调的 miRNA、923 个上调和 887 个下调的 mRNA。靶基因和 DEmRNA 主要富集在一氧化氮生物合成过程、血管加压素调节的水重吸收等过程。通过 miRNA-mRNA 网络构建，由 24 个 DEmiRNA 调控 top 30 个 hub 基因。在数据集 GSE27276 中，有 8 个基因异常表达。在 TM 和房水中，分别有 3 个基因（CREB1、CAPZA2、SLC2A3）和 2 个 miRNA（miR-106b-5p、miR-15a-5p）被鉴定为 POAG 的潜在生物标志物。GSEA 分析表明，这 3 个基因通过不同的途径调节 POAG。