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/miR196b-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.

Automated summary

In this study, a ceRNA network was constructed based on differentially expressed circRNAs, miRNAs, and mRNAs in RIF. The hsa_circ_0038383-mediated miR196b-5p/HOXA9 axis was identified as a potential key pathway in affecting RIF. This network provides new insights for exploring potential biomarkers for diagnosis and clinical treatment of RIF.