Hsa_circ_0038383-mediated competitive endogenous RNA network in recurrent implantation failure

Background: Inadequate endometrial receptivity contributes to recurrent implantation failure (RIF) during IVF–embryo transfer. Though multiple circRNAs have been confirmed differentially expression in RIF, the potential function of novel circRNAs needed to be detected. Results: The top ten DEcircRNAs were selected as initial candidates. A ceRNA network was conducted on the basis of circRNA–miRNA–mRNA potential interaction, consisting of 10 DEcircRNAs, 28 DEmiRNAs and 59 DEmRNAs. Three down-regulation circRNAs with high degree of connectivity were verified by RT-qPCR, and results suggested that only hsa_circ_0038383 was significantly downregulation in RIF compared with control group. Subsequently, three hub genes (HOXA3, HOXA9 and PBX1) were identified as hub genes. Ultimately, a subnetwork was determined based on one DEcircRNA (hsa_circ_0038383), two DEmiRNAs (has-miR-196b-5p and has-miR-424-5p), and three DEmRNAs (HOXA3, HOXA9 and PBX1). Following verification, hsa_circ_0038383/miR-196b-5p/HOXA9 axis may be a key pathway in affecting RIF. Conclusion: In summary, a hsa_circ_0038383-mediated ceRNA network related to RIF was proposed. This network provided new insight into exploring potential biomarkers for diagnosis and clinical treatment of RIF. Methods: We retrieved the expression profiles of RIF from GEO databases (circRNA, microRNA and mRNA) and constructed a competing endogenous RNAs (ceRNA) network based on predicted circRNA–miRNA and miRNA–mRNA pairs. The expression levels of three hub DEcircRNAs identified by cytoscape were validated by RT-qPCR.