Analysis of Long Noncoding RNAs-Related Regulatory Mechanisms in Duchenne Muscular Dystrophy Using a Disease-Related lncRNA-mRNA Pathway Network.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY

Genetics research Pub Date : 2022-01-01 DOI:10.1155/2022/8548804

Bing Xu, Chunlei Zheng

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Abstract

Objective: This study aimed to investigate the molecular regulatory mechanisms underpinning Duchenne muscular dystrophy (DMD).

Methods: Using microarray data, differentially expressed long noncoding RNAs (DELs) and DMD-related differentially expressed mRNAs (DEMs) were screened based on the comparative toxicogenomics database, using a cutoff of |log₂ fold change| > 1 and false discovery rate (FDR) < 0.05. Then, protein-protein interaction (PPI), coexpression network of lncRNA-mRNA, and DMD-related lncRNA-mRNA pathway networks were constructed, and functional analyses of the genes in the network were performed. Finally, the proportions of immune cells infiltrating the muscle tissues in DMD were analyzed, and the correlation between the immune cells and expression of the DELs/DEMs was studied.

Results: A total of 46 DELs and 313 DMD-related DEMs were identified. The PPI network revealed STAT1, VEGFA, and CCL2 to be the top three hub genes. The DMD-related lncRNA-mRNA pathway network comprising two pathways, nine DELs, and nine DMD-related DEMs showed that PYCARD, RIPK2, and CASP1 were significantly enriched in the NOD-like receptor signaling pathway, whereas MAP2K2, LUM, RPS6, PDCD4, TWIST1, and HIF1A were significantly enriched with proteoglycans in cancers. The nine DELs in this network were DBET, MBNL1-AS1, MIR29B2CHG, CCDC18-AS1, FAM111A-DT, GAS5, LINC01290, ATP2B1-AS1, and PSMB8-AS1.

Conclusion: The nine DMD-related DEMs and DELs identified in this study may play important roles in the occurrence and progression of DMD through the two pathways of the NOD-like receptor signaling pathway and proteoglycans in cancers.

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利用疾病相关lncRNA-mRNA通路网络分析杜氏肌营养不良的长链非编码rna相关调控机制

目的:探讨杜氏肌营养不良症(DMD)的分子调控机制。方法:利用微阵列数据，基于比较毒理学基因组学数据库筛选差异表达的长链非编码rna (DELs)和dmd相关的差异表达mrna (DEMs)，采用截断值|log2倍变化| > 1和错误发现率(FDR)。结果:共鉴定出46个DELs和313个dmd相关的DEMs。PPI网络显示STAT1、VEGFA和CCL2是前三个中心基因。dmd相关的lncRNA-mRNA通路网络包括两条通路，9条DELs和9条dmd相关的DEMs，结果表明PYCARD、RIPK2和CASP1在nod样受体信号通路中显著富集，而MAP2K2、LUM、RPS6、PDCD4、TWIST1和HIF1A在癌症中显著富集蛋白聚糖。该网络中的9个dell分别是DBET、MBNL1-AS1、MIR29B2CHG、CCDC18-AS1、FAM111A-DT、GAS5、LINC01290、ATP2B1-AS1和PSMB8-AS1。结论:本研究发现的9个DMD相关的dem和DELs可能在肿瘤中通过nod样受体信号通路和蛋白聚糖两条途径在DMD的发生和进展中发挥重要作用。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.