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原发性开角型青光眼相关潜在生物靶分子的鉴定

Identification of the potential biological target molecules related to primary open-angle glaucoma.

作者信息

Li Hongyu, Ye Zi, Li Zhaohui

机构信息

Medical School of Chinese PLA, Beijing, China.

Senior Department of Ophthalmology, the Third Medical Center of PLA General Hospital, Beijing, China.

出版信息

BMC Ophthalmol. 2022 Apr 23;22(1):188. doi: 10.1186/s12886-022-02368-0.

Abstract

BACKGROUND

To identify the potential biological target molecules and the corresponding interaction networks in primary open-angle glaucoma (POAG) development.

METHODS

The microarray datasets of GSE138125 and GSE27276 concerning lncRNA and mRNA expression profiles in trabecular meshwork of POAG were downloaded from the Gene Expression Omnibus database. The R software was applied to identify differentially expressed (DE) lncRNAs and mRNAs in POAG, and to perform GO and KEGG functional enrichment analysis. Protein-protein interaction (PPI) network and module analysis, and lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network were performed by Cytoscape software.

RESULTS

A total of 567 DE-mRNAs were identified from GSE138125 and GSE27276, including 298 up-regulated and 269 down-regulated mRNAs, which were found enriching in biological processes of extracellular matrix organization and epidermis development, respectively. KEGG pathway enrichment analysis further revealed that module genes in PPI network were primarily involved in the AGE-PAGE, PI3K-Akt and TGF-β signaling pathways. Moreover, 897 up-regulated and 1036 down-regulated DE-lncRNAs were identified from GSE138125. Through literature review and databases searching, we obtained 712 lncRNA-miRNA and 337 miRNA-mRNA pairs based on the selected eight POAG-related miRNAs. After excluding 702 lncRNAs and 284 mRNAs that were not comprised in the DE-lncRNA and DE-mRNAs, a total of 53 lncRNA nodes, eight miRNA nodes, 10 mRNA nodes, and 78 edges were included in the final ceRNA network.

CONCLUSIONS

This study demonstrated the lncRNA and mRNA expression profiles of trabecular meshwork in POAG patients and the normal controls, and identified potentially ceRNAs and pathways which might improve the pathogenic understanding of this ocular disease.

摘要

背景

识别原发性开角型青光眼(POAG)发展过程中的潜在生物靶分子及相应的相互作用网络。

方法

从基因表达综合数据库下载关于POAG小梁网中lncRNA和mRNA表达谱的GSE138125和GSE27276芯片数据集。应用R软件识别POAG中差异表达的(DE)lncRNA和mRNA,并进行GO和KEGG功能富集分析。通过Cytoscape软件进行蛋白质-蛋白质相互作用(PPI)网络和模块分析以及lncRNA-miRNA-mRNA竞争性内源RNA(ceRNA)网络分析。

结果

从GSE138125和GSE27276中总共鉴定出567个DE-mRNA,包括298个上调的和269个下调的mRNA,分别发现它们富集在细胞外基质组织和表皮发育的生物学过程中。KEGG通路富集分析进一步显示PPI网络中的模块基因主要参与AGE-PAGE、PI3K-Akt和TGF-β信号通路。此外,从GSE138125中鉴定出897个上调的和1036个下调的DE-lncRNA。通过文献综述和数据库搜索,基于所选的8个与POAG相关的miRNA,我们获得了712个lncRNA-miRNA对和337个miRNA-mRNA对。在排除DE-lncRNA和DE-mRNA中未包含的702个lncRNA和284个mRNA后,最终的ceRNA网络共包含53个lncRNA节点、8个miRNA节点、10个mRNA节点和78条边。

结论

本研究展示了POAG患者和正常对照中小梁网的lncRNA和mRNA表达谱,并鉴定出潜在的ceRNA和通路,这可能有助于增进对这种眼病发病机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/521b/9034601/b6b47baae4ff/12886_2022_2368_Fig1_HTML.jpg

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