Identification of methylation-driven genes, circulating miRNAs and their potential regulatory mechanisms in gestational diabetes mellitus

Objective: Gestational diabetes mellitus (GDM) is a major pregnancy complication. The purpose of this study is to investigate the molecular regulatory mechanisms of GDM. Methods: RNA-seq and methylation data of GDM were retrieved from the Gene Expression Omnibus database. Following principal component analysis (PCA), differentially expressed mRNAs and microRNAs (miRNAs) in the blood were highlighted between GDM and the control. Then, an abnormally expressed miRNA-mRNA network was constructed, based on which a protein-protein interaction (PPI) network was established to identify hub genes. Differentially expressed and methylated genes were identified for GDM, followed by functional enrichment analysis. Results: According to PCA results, no outlier samples were found. A total of 35 differentially expressed circulating miRNAs were identified for GDM. The miRNA-mRNA regulatory network consisted of 94 miRNA-mRNA pairs. The PPI network contained 10 hub genes, including HIF1A, TLR2, FOS, IL6R, MYLIP, ABCA1, SELL, BCL3, AP1G1 and NECAP1. Furthermore, 22 down-regulated and hypermethylated genes and 8 up-regulated and hypomethylated genes were identified for GDM, which are related to helper T cell (Th) differentiation. Conclusion: We identified methylation-driven genes and circulating miRNAs for GDM, which have the potential to serve as novel diagnostic biomarkers.