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.

摘要

目的：复发性植入失败（RIF）加重了体外受精-胚胎移植（IVF-ET）不孕女性的生理创伤。本研究目标是找出与RIF相关的关键基因、调控因子和药物靶基因。

方法：从基因表达综合数据库（GEO）获得的GSE58144数据集, 主要包含43例RIF和72例对照子宫内膜样本。首先分析RIF和对照组之间的差异表达基因（DEG）, 然后进行途径和GO富集分析。然后建立了蛋白质-蛋白质相互作用（PPI）网络和miRNA-转录因子（TF）-DEGS网络。最后, 构建了药物-靶点相互作用网络。

结果：在RIF和对照组之间共鉴定出399个DEG。在PPI和关键模块网络中, UBE2I、PLK4、XPO1、AURKB和NUP107被确定为中枢基因, 它们主要富集在RNA转运和细胞分裂周期相关途径和GO项目中。在miRNA-TF-degs网络中, E2F4、SIN3A、miRNA489、miRNA199A、miRNA369-3P、miRNA422和miRNA522被认为是RIF过程中的关键调控因子。此外, HTR1A、NR3C1和GABRA3是DrugBank注释的药物的主要靶点。

结论：PLK4、XPO1、AURKB和NUP107对RIF的影响可能是通过影响子宫内膜间质细胞的增殖和分化来实现的。此外, SIN3A和miRNA199A可能是胚胎植入的关键基因。此外, NR3C1可作为RIF临床治疗的一个可能靶点。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Recurrent implantation failure
• endometrium
• protein-protein interaction network
• miRNAs-TFs-DEGs network
• drug-target interaction
• NR3C1

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Disclosure statement

The authors declare that they have no conflicts of interest.