Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus.

Abstract

This study aimed to identify epigenetic alternations of microRNAs and DNA methylation for gestational diabetes mellitus (GDM) diagnosis and treatment using in silico approach. Data of mRNA and miRNA expression microarray (GSE103552 and GSE104297) and DNA methylation data set (GSE106099) were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated genes (DMGs) were obtained by limma package. Functional and enrichment analyses were performed with the DAVID database. The protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Simultaneously, a connectivity map (CMap) analysis was performed to screen potential therapeutic agents for GDM. In GDM, 184 low miRNA-targeting up-regulated genes and 234 high miRNA-targeting down-regulated genes as well as 364 hypomethylation-high-expressed genes and 541 hypermethylation-low-expressed genes were obtained. They were mainly enriched in terms of axon guidance, purine metabolism, focal adhesion and proteasome, respectively. In addition, 115 genes (67 up-regulated and 48 down-regulated) were regulated by both aberrant alternations of miRNAs and DNA methylation. Ten chemicals were identified as putative therapeutic agents for GDM and four hub genes (IGF1R, ATG7, DICER1 and RANBP2) were found in PPI and may be associated with GDM. Overall, this study identified a series of differentially expressed genes that are associated with epigenetic alternations of miRNA and DNA methylation in GDM. Ten chemicals and four hub genes may be further explored as potential drugs and targets for GDM diagnosis and treatment, respectively.

• Authors: Weiqiang Zhu, Yupei Shen, Junwei Liu, Xiaoping Fei, Zhaofeng Zhang, Min Li, Xiaohong Chen, Jianhua Xu, Qianxi Zhu, Weijin Zhou, Meihua Zhang, Shangqing Liu, Jing Du
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 23 Pg. 13899-13912 (12 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 33085184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• MicroRNAs
• RNA, Messenger

Topics

• Computational Biology (methods)
• CpG Islands
• DNA Methylation
• Databases, Genetic
• Diabetes, Gestational (drug therapy, etiology, metabolism)
• Drug Discovery
• Epigenesis, Genetic
• Female
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• MicroRNAs (genetics)
• Pregnancy
• Protein Interaction Mapping
• RNA Interference
• RNA, Messenger (genetics)
• Transcriptome