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氧化应激下人眼小梁细胞中 lncRNA 相关 ceRNA 网络的综合分析。

Integrative analysis of an lncRNA‑associated competing endogenous RNA network in human trabecular meshwork cells under oxidative stress.

机构信息

Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Mol Med Rep. 2020 Mar;21(3):1606-1614. doi: 10.3892/mmr.2020.10955. Epub 2020 Jan 21.

DOI:10.3892/mmr.2020.10955
PMID:32016457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7003033/
Abstract

Long non‑coding RNAs (lncRNAs) are a group of non‑coding transcripts of >200 nucleotides. They can act as competing endogenous RNAs (ceRNAs) and suppress microRNA (miRNA) function by preventing them from binding to and interacting with target mRNAs. However, the specific role of the lncRNA‑associated ceRNA network in the pathogenesis of glaucoma has not yet been elucidated. To study this, data were downloaded from the Gene Expression Omnibus database (GSE126170), which contained three human trabecular meshwork cell (HTMC) samples treated with 300 µm hydrogen peroxide and three control samples treated with vehicle. Differentially expressed lncRNAs and mRNAs of HTMCs were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of differentially expressed mRNAs were performed using the R package clusterProfiler. Finally, the ceRNA network was constructed using the mircode, miRDB, miRTarBase and TargetScan databases, and visualized using Cytoscape v3.6.1. The results showed that 70 lncRNAs and 558 mRNAs were identified to be significantly dysregulated (|log2FoldChange| >1 and adjusted P<0.05) in HTMCs under oxidative stress compared to those in HTMCs under control conditions. Moreover, 24 lncRNAs, 24 miRNAs and 40 mRNAs were closely connected, and were part of the ceRNA network. Among these, the expression levels of 19 lncRNAs were upregulated, and those of 5 lncRNAs were downregulated. To conclude, using bioinformatics analysis, the differential expression profiles of lncRNAs were reported and a lncRNA‑associated ceRNA network in HTMCs under oxidative stress was constructed. These results may bring to light a new pathological mechanism or a potential therapeutic target for glaucoma.

摘要

长链非编码 RNA(lncRNA)是一组长度大于 200 个核苷酸的非编码转录物。它们可以作为竞争性内源性 RNA(ceRNA),通过阻止 miRNA 与靶 mRNA 结合和相互作用来抑制 miRNA 的功能。然而,lncRNA 相关 ceRNA 网络在青光眼发病机制中的具体作用尚未阐明。为了研究这一点,从基因表达综合数据库(GSE126170)中下载了数据,其中包含 3 个人眼小梁细胞(HTMC)样本,用 300μM 过氧化氢处理,3 个对照样本用载体处理。使用 R 包 limma 获得 HTMC 中差异表达的 lncRNA 和 mRNA。使用 R 包 clusterProfiler 对差异表达的 mRNA 进行基因本体论和京都基因与基因组百科全书通路分析。最后,使用 mircode、miRDB、miRTarBase 和 TargetScan 数据库构建 ceRNA 网络,并使用 Cytoscape v3.6.1 可视化。结果显示,与对照条件下的 HTMC 相比,氧化应激下的 HTMC 中有 70 个 lncRNA 和 558 个 mRNA 显著失调(|log2FoldChange|>1 和调整后的 P<0.05)。此外,有 24 个 lncRNA、24 个 miRNA 和 40 个 mRNA 紧密相连,构成了 ceRNA 网络。其中,19 个 lncRNA 的表达水平上调,5 个 lncRNA 的表达水平下调。总之,通过生物信息学分析,报告了 lncRNA 的差异表达谱,并构建了氧化应激下 HTMC 中的 lncRNA 相关 ceRNA 网络。这些结果可能揭示了青光眼的新病理机制或潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/7003033/9a728953ba17/MMR-21-03-1606-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/7003033/9a728953ba17/MMR-21-03-1606-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731c/7003033/9a728953ba17/MMR-21-03-1606-g02.jpg

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