Research Paper Volume 13, Issue 4 pp 6076—6090

Hsa_circ_0038383-mediated competitive endogenous RNA network in recurrent implantation failure

Huishan Zhao1, *, , Lili Chen1, *, , Yinghua Shan1, *, , Gang Chen2, , Yongli Chu3, , Huangguan Dai1, , Xuemei Liu1, , Hongchu Bao1, ,

  • 1 Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
  • 2 Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
  • 3 Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
* Equal contribution

Received: September 5, 2020       Accepted: December 19, 2020       Published: February 20, 2021
How to Cite

Copyright: © 2021 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


GEO: Gene Expression Omnibus; RIF: recurrent implantation failure; IVF–ET: in vitro fertilization-embryo transfer; ART: assisted reproductive technology; circRNAs: circular RNAs; DEcircRNAs: differently expressed circRNAs; DEmiRNAs: differently expressed miRNAs; DEmRNAs: differently expressed mRNAs; ceRNA: competing endogenous RNAs; ncRNAs: non-coding RNAs; RT-qPCR: real-time quantitative polymerase chain reaction; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Gene and Genome; STRING: the Search Tool for the Tetrieval of Interacting Genes database; PPI: protein-protein interaction; MCODE: Molecular Complex Detection; RBPs: RNA-binding proteins.