Abstract
BackgroundThis study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM).MethodsThe GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA–transcription factor (TF)–DEG regulatory network was analyzed.ResultsIn total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted.ConclusionsFour candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.
Highlights
This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM)
Analysis of the differentially expressed genes After the microarray analysis, the probes that were mapped to multiple genes were considered nonspecific and were removed, and only those with unique genes were distinguished as DEGs
Functional enrichment analyses Through Gene Ontology (GO) analysis, the top 10 overrepresented GO terms in the biological process (BP), molecular function (MF), and cellular component (CC) categories were identified on the basis of the p-value (Fig. 2a)
Summary
This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM). Expectant mothers with gestational diabetes mellitus (GDM), a common pregnancy complication, have an increased risk of developing type 2 diabetes mellitus [1]. Babies born to mothers with GDM are typically at a high risk for macrosomia, neonatal cardiac dysfunction, neonatal hypoglycemia, stillbirth, childhood obesity, and type 2 diabetes mellitus [4,5,6]. Given the worldwide prevalence and adverse outcomes of GDM, Previous studies have suggested that GDM is caused by enhanced insulin resistance and pancreatic beta (β)cell dysfunction [7], involving genes that are related to insulin signaling, insulin secretion, maturity-onset diabetes of the young, and lipid and glucose metabolism, to name a few [8, 9]. GDM results in major changes in the expression profiles of placental genes, with a
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