Deciphering key circRNA-miRNA-mRNA network involved in premature ovarian insufficiency by whole transcriptome sequencing

Premature ovarian insufficiency (POI) is a severe disorder caused by ovarian damage. Until now the regulatory network of circular RNA (circRNA) associated with premature ovarian failure is not wholly understood. In this study, whole transcriptome sequencing of ovarian cortex tissue from normal donors (ctrl group) and POI patients (POI group), and cultured POI ovarian cortical fragments (IVA group) were performed to investigate the differentially expressed circRNAs (DEcircRNAs), miRNA (DEmiRNAs) and mRNA (DEmRNAs). By constructing a circRNA-miRNA-mRNA competing endogenous RNAs (ceRNA) network, a total of 134 and 247 DEcircRNAs were found in POI group and IVA group, respectively, compared with control group. KEGG enrichment analysis demonstrated that the host genes of DEcircRNAs mainly involved in the mTOR pathway, NOD-like receptor signaling pathway and Rap1 signaling pathway. Compared with ctrl group, up to 76 DEmiRNAs were identified in POI group, and 110 DEmiRNAs in IVA group. The DEmiRNAs were mainly involved in Notch pathway, WNT pathway and Hepatocellular receptor signaling pathway. 415 and 4517 DEmRNAs were appeared in the POI and IVA groups, respectively, compared with the control group. These DEmRNAs were mainly participate in cell adhesion, PI3K-Akt signaling pathway and Rap1 signaling pathway. In ceRNA network, the target gene of DEcircRNA mainly participated in mTOR signaling pathway, Nod-like signaling pathway, and Hippo signaling pathway, which were related to fibrosis and chronic inflammation. Moreover, SERPINE1 is deferentially expressed in the comparison between groups and mediates Hippo signaling pathway. Taken together, this study provides a ceRNA Pathway of circRNA-miRNA-mRNA driving POI.