Identification of human placenta-derived circular RNAs and autophagy related circRNA-miRNA-mRNA regulatory network in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a metabolic and reproductive disease with serious risks and adverse health effects. However, the pathophysiological mechanism of GDM, especially the roles of circRNAs in its pathogenesis, is largely unknown. The objective of this study was to identify and investigate the roles of circRNAs in GDM. In the current study, placental circRNA expression profiles of normal controls and GDM patients were analyzed using high-throughput sequencing. Bioinformatics analysis identified a total of 4,955 circRNAs, of which 37 circRNAs were significantly deregulated in GDM placentas compared with NC placentas. GO and KEGG enrichment analyses demonstrated that metabolic process-associated terms and metabolic pathways that may be related to GDM were significantly enriched. The biological characteristics of placenta-derived circRNAs, such as their stability and RNase R resistance, were also validated Bioinformatics prediction. Moreover, we constructed the autophagy related circRNA-miRNA-mRNA regulatory network and further functional analysis revealed that the circCDH2–miR-33b-3p–ULK1 axis may be associated with autophagy in the placentas of GDM patients. Our study indicates that aberrant expression of circRNAs may play roles in autophagy in GDM placentas, providing new insights into GDM.