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Comprehensive Analysis of Long Non-coding RNA-Associated Competing Endogenous RNA Network in Duchenne Muscular Dystrophy

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Abstract

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.

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Funding

This work was kindly supported by National Natural Science Foundation of China (81601129) and Science Foundation of Shenyang (F16-205-1-48).

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Authors and Affiliations

  1. Department of Neurology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Xiaoxue Xu, Yuehan Hao & Zhiyi He

  2. Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, 110001, China

    Xiaoxue Xu, Yuehan Hao & Zhiyi He

  3. Liaoning Academy of Analytic Science, Construction Engineering Center of Important Technology Innovation and Research and Development Base in Liaoning Province, Shenyang, 110015, China

    Shuang Xiong

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Xu, X., Hao, Y., Xiong, S. et al. Comprehensive Analysis of Long Non-coding RNA-Associated Competing Endogenous RNA Network in Duchenne Muscular Dystrophy. Interdiscip Sci Comput Life Sci 12, 447–460 (2020). https://doi.org/10.1007/s12539-020-00388-2

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