RT Journal Article
SR Electronic
T1 Identifying the potential transcriptional regulatory network in Hirschsprung disease by integrated analysis of microarray datasets
JF World Journal of Pediatric Surgery
JO World Jnl Ped Surgery
FD BMJ Publishing Group Ltd
SP e000547
DO 10.1136/wjps-2022-000547
VO 6
IS 2
A1 Xu, Wenyao
A1 Yu, Hui
A1 Chen, Dian
A1 Pan, Weikang
A1 Yang, Weili
A1 Miao, Jing
A1 Jia, Wanying
A1 Zheng, Baijun
A1 Liu, Yong
A1 Chen, Xinlin
A1 Gao, Ya
A1 Tian, Donghao
YR 2023
UL http://wjps.bmj.com/content/6/2/e000547.abstract
AB Objective Hirschsprung disease (HSCR) is one of the common neurocristopathies in children, which is associated with at least 20 genes and involves a complex regulatory mechanism. Transcriptional regulatory network (TRN) has been commonly reported in regulating gene expression and enteric nervous system development but remains to be investigated in HSCR. This study aimed to identify the potential TRN implicated in the pathogenesis and diagnosis of HSCR.Methods Based on three microarray datasets from the Gene Expression Omnibus database, the multiMiR package was used to investigate the microRNA (miRNA)–target interactions, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF–miRNA–mRNA regulatory network and used cytoHubba to identify the key modules. Finally, the receiver operating characteristic (ROC) curve was determined and the integrated diagnostic models were established based on machine learning by the support vector machine method.Results We identified 58 hub differentially expressed microRNAs (DEMis) and 16 differentially expressed mRNAs (DEMs). The robust target genes of DEMis and DEMs mainly enriched in several GO/KEGG terms, including neurogenesis, cell–substrate adhesion, PI3K–Akt, Ras/mitogen-activated protein kinase and Rho/ROCK signaling. Moreover, 2 TFs (TP53 and TWIST1), 4 miRNAs (has-miR-107, has-miR-10b-5p, has-miR-659-3p, and has-miR-371a-5p), and 4 mRNAs (PIM3, CHUK, F2RL1, and CA1) were identified to construct the TF–miRNA–mRNA regulatory network. ROC analysis revealed a strong diagnostic value of the key TRN regulons (all area under the curve values were more than 0.8).Conclusion This study suggests a potential role of the TF–miRNA–mRNA network that can help enrich the connotation of HSCR pathogenesis and diagnosis and provide new horizons for treatment.Data are available in a public, open access repository. Publicly available datasets (GSE96854, GSE98502, and GSE77296) were analyzed in this study. All the datasets can be found in the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/).