Duchenne muscular dystrophy (DMD) is one of the most severe neuromuscular disorders. Long non-coding RNAs (lncRNAs) are a group of non-coding transcripts, which could regulate messenger RNA (mRNA) by binding the mutual miRNAs, thus acting as competing endogenous RNAs (ceRNAs). So far, the role of lncRNA in DMD pathogenesis remains unclear. In the current study, expression profile from a total of 33 DMD patients and 12 healthy people were downloaded from Gene Expression Omnibus (GEO) database (GSE38417 and GSE109178). Differentially expressed (DE) lncRNAs were discovered and targeted mRNAs were predicted. The ceRNA network of lncRNAs—miRNAs—mRNAs was then constructed. Genome Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the putative mRNAs in the ceRNA network were performed through Database for Annotation, Visualization and Integration Discovery (DAVID) website. Topological property of the network was analyzed using Cytoscape to disclose the hub lncRNAs. According to our assessments, 19 common DElncRNAs and 846 common DEmRNAs were identified in DMD compared to controls. The created ceRNA network contained 6 lncRNA nodes, 69 mRNA nodes, 27 miRNA nodes and 102 edges, while four hub lncRNAs (XIST, AL132709, LINC00310, ALDH1L1-AS2) were uncovered. In conclusion, our latest bioinformatic analysis demonstrated that lncRNA is likely involved in DMD. This work highlights the importance of lncRNA and provides new insights for exploring the molecular mechanism of DMD.

Graphic abstract

The created ceRNA network contained 6 lncRNA nodes, 69 mRNA nodes, 27 miRNA nodes and 102 edges, while four hub lncRNAs (XIST, AL132709, LINC00310, ALDH1L1-AS2) were uncovered. Remarkably, KEGG analysis indicated that targeted mRNAs in the network were mainly enriched in “microRNAs in cancer” and “proteoglycans in cancer”. Our study may offer novel perspectives on the pathogenesis of DMD from the point of lncRNAs. This work might be also conducive for exploring the molecular mechanism of increased incidence of tumorigenesis reported in DMD patients and experimental models.

中文翻译：

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杜氏肌营养不良症中长链非编码 RNA 相关竞争性内源性 RNA 网络的综合分析。

杜氏肌营养不良症 (DMD) 是最严重的神经肌肉疾病之一。长链非编码 RNA (lncRNA) 是一组非编码转录物，可以通过结合相互的 miRNA 来调节信使 RNA (mRNA)，从而充当竞争性内源 RNA (ceRNA)。到目前为止，lncRNA 在 DMD 发病机制中的作用仍不清楚。在目前的研究中，从基因表达综合 (GEO) 数据库 (GSE38417 和 GSE109178) 下载了总共 33 名 DMD 患者和 12 名健康人的表达谱。发现了差异表达 (DE) lncRNA 并预测了靶向 mRNA。然后构建了lncRNAs-miRNAs-mRNAs的ceRNA网络。ceRNA 网络中假定的 mRNA 的基因组本体论 (GO) 富集和京都基因和基因组百科全书 (KEGG) 通路分析是通过注释、可视化和集成发现数据库 (DAVID) 网站进行的。使用 Cytoscape 分析网络的拓扑特性以公开中枢 lncRNA。根据我们的评估，与对照相比，在 DMD 中鉴定了 19 种常见的 DElncRNA 和 846 种常见的 DEmRNA。创建的 ceRNA 网络包含 6 个 lncRNA 节点、69 个 mRNA 节点、27 个 miRNA 节点和 102 个边，而四个中枢 lncRNA（XIST、AL132709、LINC00310、ALDH1L1-AS2）被发现。总之，我们最新的生物信息学分析表明 lncRNA 可能参与 DMD。这项工作突出了 lncRNA 的重要性，并为探索 DMD 的分子机制提供了新的见解。

图形摘要

创建的 ceRNA 网络包含 6 个 lncRNA 节点、69 个 mRNA 节点、27 个 miRNA 节点和 102 条边，同时发现了 4 个中枢 lncRNA（XIST、AL132709、LINC00310、ALDH1L1-AS2）。值得注意的是，KEGG 分析表明，网络中的靶向 mRNA 主要富含“癌症中的 microRNA”和“癌症中的蛋白多糖”。我们的研究可能会从 lncRNA 的角度为 DMD 的发病机制提供新的视角。这项工作也可能有助于探索 DMD 患者和实验模型中报告的肿瘤发生率增加的分子机制。