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Construction of hub transcription factor–microRNAs–messenger RNA regulatory network in recurrent implantation failure

  • Reproductive physiology and disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Recurrent implantation failure (RIF) affects up to 10% of in vitro fertilization (IVF) patients worldwide. However, the pathogenesis of RIF remains unclear. This study was aimed at identifying hub transcription factors (TFs) of RIF in bioinformatics approaches.

Methods

The GSE111974 (mRNA), GSE71332 (miRNA), and GSE103465 (mRNA) datasets were downloaded from the Gene Expression Omnibus database from human endometrial tissue using R version 4.2.1 and used to identify differentially expressed TFs (DETFs), differentially expressed miRNAs, and differentially expressed genes for RIF, respectively. DETFs were subjected to functional enrichment analysis and the protein–protein interaction network analysis using the Search Tool for the Retrieval of Interacting Genes (version 11.5) database. Hub TFs were identified using the cytoHubb plug-in, after which a hub TF–miRNA–mRNA network was constructed using Cytoscape v3.8.2.

Results

Fifty-seven DETFs were identified, in which Gene Ontology analysis revealed to be mainly involved in the regulation of transcription. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that DETFs were enriched in transcriptional misregulation in cancer, aldosterone synthesis and secretion, AMPK signaling pathway, and cGMP-PKG signaling pathway. EOMES, NKX2-1, and POU5F1 were identified as hub TFs, and a hub TF–miRNA–mRNA regulatory network was constructed using these three hub TFs, four miRNAs, and four genes.

Conclusion

Collectively, we identified three promising molecular biomarkers for the diagnosis of RIF, which may further be potential therapeutic targets. This study provides novel insights into the molecular mechanisms underlying RIF. However, further experiments are required to verify these results.

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Data availability

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

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Funding

This manuscript was supported by the National Natural Science Foundation of China (grant number 81860271 and 82160281), Yunnan Ten Thousand Talents Program for Famous Doctors and Masters (grant number Yunwei Renfa [2019] No. 35), Yunnan Support Program of High Level Talents Cultivation Famous Medical Project (grant number RLMY20200017), Fundamental Research Joint Project of Local Undergraduate Universities in Yunnan Province (grant number 2020D1BA07000), Yunnan Provincial Clinical Medical Center for Reproductive Obstetrics and Gynecology (grant number zx209-01-01), Open Subject of Yunnan Clinical Medical Center for Reproductive and Maternal Diseases (grant number 2019LCZXKF-SZ04), Dali Science and Technology Planning Project (grant numbers 2021085 and 2021086), and Open Program of Clinical Medical Center of First People’s Hospital of Yunnan Province (2022LCZXKF-SZ13).

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Author notes

  1. Jiahuan Luo, Rongxia Huang, and Pengying Xiao have contributed equally to this work.

Authors and Affiliations

  1. Department of Reproductive Genetics, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, China

    Jiahuan Luo & Li Tang

  2. Department of Reproductive Medicine, The First Affiliated Hospital of Dali University, Dali, China

    Jiahuan Luo, Anli Xu, Zhaomei Dong, Lirong Zhang, Rui Wu, Yunlin Qiu & Li Zhu

  3. Innovation Team in Reproductive Medicine, Dali University, No. 32, Carlsberg Avenue, Dali, Yunnan, China

    Jiahuan Luo, Anli Xu, Zhaomei Dong, Lirong Zhang & Li Zhu

  4. First Clinical Medical College, Kunming Medical University, Kunming, China

    Jiahuan Luo & Li Tang

  5. Department of Gynecology, Kunming Maternal and Child Health Hospital, Kunming, China

    Rongxia Huang

  6. Reproductive Medicine Center, Dongguan Songshan Lake Central Hospital, Dongguan, 523429, China

    Pengying Xiao & Ruopeng Zhang

  7. Reproductive Medicine Center, Kunming Maternal and Child Health Hospital, No. 43, Huashan West Road, Huashan Street, Wuhua District, Kunming, China

    Anli Xu, Zhaomei Dong, Lirong Zhang, Rui Wu, Yunlin Qiu, Li Zhu & Ruopeng Zhang

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  1. Jiahuan Luo
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  2. Rongxia Huang
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Contributions

Conceptualization: JL, RH, and PX. Formal analysis: AX, ZD, LZ, RW, YQ, and LZ. Methodology: RH, PX, AX, ZD, LZ, RW, YQ, and LZ. Software: JL, AX, and ZD. Supervision: RZ and LT. Writing—original draft, JL, RH, and PX. Writing—review and editing: LZ, RZ, and LT. Project administration: RZ and LT. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li Zhu, Ruopeng Zhang or Li Tang.

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Publicly available datasets were analyzed in this study, so ethical review, approval, and written informed consent for participation were not required for the study.

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Luo, J., Huang, R., Xiao, P. et al. Construction of hub transcription factor–microRNAs–messenger RNA regulatory network in recurrent implantation failure. J Assist Reprod Genet 41, 3–13 (2024). https://doi.org/10.1007/s10815-023-02947-0

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