Identification of hub genes, miRNAs and regulatory factors relevant for Duchenne muscular dystrophy by bioinformatics analysis
Identification of hub genes, miRNAs and regulatory factors relevant for Duchenne muscular dystrophy by bioinformatics analysis
复制标题
通过生物信息学分析鉴定与杜氏肌营养不良症相关的枢纽基因、miRNA 和调控因子
DOI：
10.1080/00207454.2020.1810030
复制
发表时间：
2020-08
影响因子：
2.2
通讯作者：
Kuang Bo-Hai
中科院分区：
文献类型：
--
作者：
Xiu Meng-Xi;Zeng Bin;Kuang Bo-Hai
摘要目的杜氏肌营养不良症（DMD）是目前最常见的由肌营养不良蛋白基因突变引起的肌营养不良症。然而，其病理过程尚不清楚，缺乏特异性的分子生物标志物。我们研究的目的是探索DMD进展背后的关键调控联系。材料和方法从gene expression Omnibus （GEO）数据库中获取DMD基因表达谱数据集GSE38417。利用geo2R筛选DMD患者与健康对照之间的差异表达基因（DEGs），然后进行京都基因与基因组百科全书（KEGG）和基因本体（GO）途径富集分析。然后构建了蛋白质-蛋白质相互作用（PPI）网络和模块子网络。为了研究DMD的调控网络，我们构建了一个包括miRNAs、mrna和转录因子（tf）在内的全球三重网络。结果DMD组与对照组共发现1811个deg，其中HERC5、SKP2和FBXW5在PPI网络中被定义为枢纽基因，连接程度为bbb35。此外，我们还发现ZNF362、ATAT1、SPI1、TCF12和ABCF2这5个tf以及miR-124a、miR-200b/200c/429、miR-19a/b、miR-23a/b、miR-182、miR-144、miR-498和miR-18a/b这8个mirna在DMD的分子发病机制中发挥着至关重要的作用。本文为DMD背后的miRNA-TF-mRNA共调控网络提供了一个全面的视角，尽管这些生物信息学研究结果需要在未来的研究中进一步验证。
Abstract Purpose Duchenne muscular dystrophy (DMD) is currently the most commonly diagnosed form of muscular dystrophy due to mutations in the dystrophin gene. However, its pathological process remains unknown and there is a lack of specific molecular biomarkers. The aim of our study is to explore key regulatory connections underlying the progression of DMD. Materials and methods The gene expression profile dataset GSE38417 of DMD was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DMD patients and healthy controls were screened using geo2R, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Then a protein–protein interaction (PPI) network and sub-network of modules were constructed. To investigate the regulatory network underlying DMD, a global triple network including miRNAs, mRNAs and transcription factors (TFs) was constructed. Results A total of 1811 DEGs were found between the DMD and control groups, among which HERC5, SKP2 and FBXW5 were defined as hub genes with a degree of connectivity >35 in the PPI network. Furthermore, the five TFs ZNF362, ATAT1, SPI1, TCF12 and ABCF2, as well as the eight miRNAs miR-124a, miR-200b/200c/429, miR-19a/b, miR-23a/b, miR-182, miR-144, miR-498 and miR-18a/b were identified as playing crucial roles in the molecular pathogenesis of DMD. Conclusions This paper provides a comprehensive perspective on the miRNA–TF–mRNA co-regulatory network underlying DMD, although the bioinformatic findings need further validation in future studies.
登录
查看更多内容
影响因子：
3.7
作者：
Parolo S;Marchetti L;Lauria M;Misselbeck K;Scott-Boyer MP;Caberlotto L;Priami C
通讯作者：
Priami C
影响因子：
4.6
作者：
Mercatelli N;Fittipaldi S;De Paola E;Dimauro I;Paronetto MP;Jackson MJ;Caporossi D
通讯作者：
Caporossi D
影响因子：
5.3
作者：
Parker, Maura H.;Perry, Robert L. S.;Rudnicki, Michael A.
通讯作者：
Rudnicki, Michael A.
影响因子：
14.9
作者：
Ninfali C;Siles L;Darling DS;Postigo A
通讯作者：
Postigo A
DOI：
10.1002/jcsm.12296
发表时间：
2018-08
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Zhang A;Li M;Wang B;Klein JD;Price SR;Wang XH
通讯作者：
Wang XH