Construction of a long non-coding RNA-mediated competitive endogenous RNA network reveals global patterns and regulatory markers in gestational diabetes

摘要

Gestational diabetes mellitus (GDM) is a common disease affecting pregnant women. Recent studies have suggested that competing endogenous RNAs (ceRNAs), which compete with long non-coding RNAs (lncRNAs) for microRNA (miRNA or miR) binding and indirectly regulate miRNA targets through competing interactions, play a critical role in disease. In this study, we present a computationally integrated approach with which to construct a lncRNA-mediated ceRNA network (LCEN) in GDM by integrating RNA interactions and expression data. lncRNAs exhibited specific features and played critical roles in GDM-associated LCEN. The construction of a global functional score profile revealed that ceRNAs had a high activity in GDM. We extracted several ceRNA modules and demonstrated that these modules had increased close interactions. We further discovered that these ceRNA modules may be utilized as specific and effective circulating biomarkers for GDM. Finally, functional analyses demonstrated that the GDM-associated ceRNAs participated in the regulation of irisin and the thyroid hormone signaling pathway. It was suggested that there were close associations between the thyroid hormone and GDM. Collectively, ceRNAs may accelerate biomarker discovery and therapeutic development in GDM.