Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing, People's Republic of China.
Chongqing Key Laboratory of Complex Systems and Bionic Control, Chongqing University of Posts and Telecommunications, Chongqing, People's Republic of China.
Comb Chem High Throughput Screen. 2023;26(3):576-588. doi: 10.2174/1386207325666220610122114.
The competing endogenous RNA (ceRNA) network plays an important role in the occurrence and development of a variety of diseases. This study aimed to construct a ceRNA network related to exosomes in diabetic retinopathy (DR).
We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of samples to obtain differentially expressed lncRNAs (DELs), miRNAs (DEMs) and mRNAs (DEGs) alongside the progress of DR. Next, Gene Set Enrichment Analysis (GSEA) analysis of DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of up-DEGs were performed. In addition, a ceRNA network related to exosomes in DR was constructed on the base of DELs, DEMs and DEGs. Finally, the function of the ceRNA network was explored by GO and KEGG enrichment analysis.
Through our analysis, 267 DELs (93 up and 174 down), 114 DEMs (64 up and 50 down) and 2368 DEGs (1252 up and 1116 down) were screened. The GSEA analysis results show that these genes were mainly related to cytokine-cytokine receptor interaction, hippo signaling pathway and JAK-STAT signaling pathway. The GO and KEGG results show that these up-DEGs were mainly enriched in viral gene expression, components of ribosomes, mineral absorption, Wntprotein binding, and TGF-β signaling pathway. Besides, a ceRNA network, including 15 lncRNAs (e.g., C1orf145, FGF14-IT1, and PRNT), 3 miRNAs (miR-10a-5p, miR-1297 and miR-507) and 11 mRNAs (NCOR2, CHAC1 and LIX1L, etc.) was constructed. Those 5 lncRNAs were up-regulated, 1 miRNA was down-regulated and 5 mRNAs were up-regulated in DR, while 10 lncRNAs were downregulated, 2 miRNAs were up-regulated and 6 mRNAs were down-regulated in DR.
The novel ceRNA network that we constructed will provide new insights into the underlying molecular mechanisms of exosomes in DR.
竞争内源性 RNA（ceRNA）网络在多种疾病的发生和发展中起着重要作用。本研究旨在构建糖尿病视网膜病变（DR）相关的外泌体 ceRNA 网络。
我们从基因表达综合数据库（GEO）中挖掘了与 DR 进展相关的样本的 RNA，以获得差异表达的长链非编码 RNA（lncRNA）（DEL）、微小 RNA（miRNA）（DEM）和信使 RNA（mRNA）（DEG）。然后，对 DEG 进行基因集富集分析（GSEA）分析、上调 DEG 的基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，在 DEL、DEM 和 DEG 的基础上构建了 DR 相关的外泌体 ceRNA 网络。最后，通过 GO 和 KEGG 富集分析探讨 ceRNA 网络的功能。
通过分析，筛选出 267 个 DEL（93 个上调，174 个下调）、114 个 DEM（64 个上调，50 个下调）和 2368 个 DEG（1252 个上调，1116 个下调）。GSEA 分析结果表明，这些基因主要与细胞因子-细胞因子受体相互作用、 Hippo 信号通路和 JAK-STAT 信号通路有关。GO 和 KEGG 结果表明，这些上调的 DEG 主要富集在病毒基因表达、核糖体成分、矿物质吸收、Wnt 蛋白结合和 TGF-β 信号通路。此外，构建了包括 15 个 lncRNA（如 C1orf145、FGF14-IT1 和 PRNT）、3 个 miRNA（miR-10a-5p、miR-1297 和 miR-507）和 11 个 mRNA（NCOR2、CHAC1 和 LIX1L 等）在内的 ceRNA 网络。在 DR 中，这 5 个 lncRNA 上调，1 个 miRNA 下调，11 个 mRNA 上调，而在 DR 中，10 个 lncRNA 下调，2 个 miRNA 上调，6 个 mRNA 下调。
我们构建的新型 ceRNA 网络将为外泌体在 DR 中的潜在分子机制提供新的见解。
