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生物信息学分析人类糖尿病性视网膜病变中的免疫浸润,鉴定免疫相关枢纽基因及其 ceRNA 网络。

Bioinformatics analysis of immune infiltration in human diabetic retinopathy and identification of immune-related hub genes and their ceRNA networks.

机构信息

Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, 650032, Yunnan, China.

Department of Emergency Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.

出版信息

Sci Rep. 2024 Oct 14;14(1):24003. doi: 10.1038/s41598-024-75055-3.

Abstract

Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients, and recent studies have shown that immune regulatory mechanisms are closely associated with retinal damage in DR. Therefore, this study focused on exploring immune cells and immune-related genes (IRGs) in DR and gaining insight into the ceRNA mechanisms by which IRGs regulate DR progression. Four datasets from human DR model retinal tissues were obtained from the Gene Expression Omnibus (GEO) database. R software was first used to identify differentially expressed mRNAs (DE-mRNAs) in the dataset GSE160306-mRNAs, then the distribution of immune cells in the gene matrix was analyzed by xCell and ImmuCellAI, ImmPort and InnateDB database were used to obtain immune-related hub genes (IRHGs) in the DR, and finally the STRING online tool and Cytoscape to construct the immune-related ceRNA network. The datasets GSE102485, GSE160308 and GSE160306-lncRNAs were used to validate the results of the ceRNA network further. The results of immune cell infiltration analysis showed that macrophages are important immune cells in DR; immune-related gene screening showed that FCGR2B is an IRHG in DR, and 2 immune-related ceRNA networks of IRHG were obtained: DDN-AS1/miR-10a-5p/FCGR2B and LINC01515/miR-10a-5p/FCGR2B. Our study suggests that infiltration of immune cells, especially the immune role of macrophages, is an important component of DR progression; the immune-related hub gene FCGR2B and its ceRNA network may be a key regulatory network for DR progression. The discovery of key immune cells, IRHG and ceRNA networks in this study may provide new prospects for early intervention and targeted treatment of DR.

摘要

糖尿病性视网膜病变(DR)是糖尿病患者最常见的微血管并发症,最近的研究表明,免疫调节机制与 DR 中的视网膜损伤密切相关。因此,本研究专注于探索 DR 中的免疫细胞和免疫相关基因(IRGs),并深入了解 IRGs 调节 DR 进展的 ceRNA 机制。从基因表达综合数据库(GEO)中获得了 4 个人类 DR 模型视网膜组织数据集。首先使用 R 软件识别数据集 GSE160306-mRNAs 中的差异表达 mRNA(DE-mRNAs),然后通过 xCell 和 ImmuCellAI 分析基因矩阵中的免疫细胞分布,使用 ImmPort 和 InnateDB 数据库获取 DR 中的免疫相关枢纽基因(IRHGs),最后使用 STRING 在线工具和 Cytoscape 构建免疫相关 ceRNA 网络。进一步使用数据集 GSE102485、GSE160308 和 GSE160306-lncRNAs 验证 ceRNA 网络的结果。免疫细胞浸润分析结果表明,巨噬细胞是 DR 中的重要免疫细胞;免疫相关基因筛选表明,FCGR2B 是 DR 中的一个 IRHG,获得了 2 个 IRHG 的免疫相关 ceRNA 网络:DDN-AS1/miR-10a-5p/FCGR2B 和 LINC01515/miR-10a-5p/FCGR2B。本研究表明,免疫细胞的浸润,特别是巨噬细胞的免疫作用,是 DR 进展的重要组成部分;免疫相关枢纽基因 FCGR2B 及其 ceRNA 网络可能是 DR 进展的关键调控网络。本研究中关键免疫细胞、IRHG 和 ceRNA 网络的发现可能为 DR 的早期干预和靶向治疗提供新的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9e/11473686/82d1fe0eda14/41598_2024_75055_Fig1_HTML.jpg

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