Expression Of CircRNAs In Placenta Of Patients With Gestational Diabetes Mellitus

ObjectiveGestational diabetes mellitus?GDM?refers to the abnormal glucose metabolism found or occurring during pregnancy,which is harmful to both pregnant women and newborns.Circular RNA?circRNA?is a special non-coding RNA with evolutionary conservation,structural stability and tissue specificity.circRNA is widely involved in the cellular metabolic regulation network.Studies have confirmed that it plays an important role in the development of tumors,nervous system diseases,atherosclerosis,diabetes,etc.It is expected to become a new early diagnostic marker and potential therapeutic target for various diseases..However,there are few reports on circRNA and gestational diabetes.The purpose of this study is to discover the differential expression of circular RNA?circRNA?in placenta of pregnant gestational diabetes?GDM?and placenta of normal pregnancy by RNA sequencing.To explore its biological functions,in order to provide new potential molecular markers and targets for early diagnosis and treatment of GDM.MethodsThe study included 45 pregnant women undergoing cesarean section,of which 30 were gestational diabetes mellitus and 15 were normal pregnant women.Differentially expressed circRNA in the placenta was identified by RNA sequencing.GO enrichment and KEGG signaling pathway analysis differentially expressed circRNA may be involved in cellular biological processes,molecular functions and cellular components as well as involved cellular signaling pathways.qRT-PCR validates differentially expressed circRNAs in more clinical samples,and further bioinformatics predicts the interaction of miRNAs,preliminarily exploring the potential biological functions of differentially expressed circRNAs.ResultsThis study identified a total of 8321 circRNAs in GDM and normal pregnant placenta.Of these,7804 circRNAs have been reported in the database,and 517 circRNAs have been newly identified.Compared with the control group,46 circRNAs were differentially expressed in placental tissues of GDM pregnant women?FC>2 and P<0.05?,of which 3 circRNAs were up-regulated and 43 expressions were significantly decreased.GO and KEGG enrichment analysis of differentially expressed circRNA-derived genes revealed that these differentially expressed circRNAs may be associated with certain biological processes?such as regulation of the SMO signaling pathway?,cellular components?such as nuclear spots,transcriptional repressor complexes?and molecules Functions such as SUMO/Ubiquitin-like binding are related.The results of KEGG analysis suggest that these differentially expressed CRC genes are involved in focal adhesion,Shigella,epithelial bacterial invasion,endocrine resistance,and advanced glycation end product receptor pathway?AGE-RAGE?,especially The AGE-RAGE signaling pathway has been shown to play an important role in a variety of diabetic complications and is associated with adverse pregnancy outcomes in GDM.The expression of circRNA₀395,circRNA₃636 and circRNA₅824 was consistent with RNA-seq by qRT-PCR and the expression was significantly decreased in the GDM group compared with the control group.CircRNA-miRNA interaction analysis suggested that circRNA₀395 has binding sites with 88 miRNAs,and the three miRNAs with the highest software prediction scores are hsa-miR-8485,hsa-miR-3135b and hsa-miR-1273g-3p,circRNA₃636 and circRNA₅824 has 3 and 8 miRNA binding sites.Based on the mechanism of action of the molecular sponge,we also mapped the circRNA-miRNA-mRNA interaction network.ConclusionWe initially explored the differential expression of circRNA in placenta of pregnant women with GDM.These poor circRNAs are involved in many important biological functions and signaling pathways and may be potentially linked to the development of GDM.