Identification of key genes, regulatory factors, and drug target genes of recurrent implantation failure (RIF)

Abstract

Objective: Recurrent implantation failure (RIF) exacerbates the physical trauma of infertile women that undergone in vitro fertilization-embryo transfer (IVF-ET). We aimed to identify the key genes, regulatory factors, and drug target genes involved in the RIF.Methods: The dataset GSE58144 that obtained from the Gene Expression Omnibus mainly contained 43 RIF and 72 control endometrial samples. Differently expressed genes (DEGs) between RIF and control groups were firstly analyzed, followed by the pathway and Gene Ontology (GO) enrichment analysis. Then, protein-protein interaction (PPI) network and miRNA-transcript factor (TF)-DEGs network were established. Finally, a drug-target interaction network was constructed.Results: A total of 399 DEGs were identified between the RIF and controls. In the PPI and key module network, UBE2I, PLK4, XPO1, AURKB, and NUP107 were identified as the hub genes, which mainly enriched in RNA transport and cell division cycle-related pathways and GO items. In the miRNA-TF-DEGs network, E2F4, SIN3A, miRNA489, miRNA199A, miRNA369-3P, miRNA422, and miRNA522 were considered as the key regulatory factors during RIF. In addition, HTR1A, NR3C1, and GABRA3 were the main targets of the drugs annotated in DrugBank.Conclusion: The effects of PLK4, XPO1, AURKB, and NUP107 on the RIF may be via affecting the proliferation and differentiation of endometrial stromal cells. Besides, SIN3A and miRNA199A may be crucial for embryo implantation. In addition, NR3C1 may be used as a possible target for the clinical therapy of RIF.

Keywords: NR3C1; Recurrent implantation failure; drug-target interaction; endometrium; miRNAs-TFs-DEGs network; protein-protein interaction network.