Construction of Circular RNA-MicroRNA-Messenger RNA Regulatory Network of Recurrent Implantation Failure to Explore Its Potential Pathogenesis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33664765", "kind": "science-record", "revision": 8, "content_hash": "sha256:7ae6979e1a7ed2ea5890aaee0363a98bbbf54be08df543fc6bdb2f02011bf79b", "created_at": "2026-11-01T15:41:27Z", "updated_at": "2026-11-01T22:46:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of Circular RNA-MicroRNA-Messenger RNA Regulatory Network of Recurrent Implantation Failure to Explore Its Potential Pathogenesis.", "doi": "10.3389/fgene.2020.627459", "pmid": "33664765", "authors": ["Jiahuan Luo", "Li Zhu", "Ning Zhou", "Yuanyuan Zhang", "Lirong Zhang", "Ruopeng Zhang"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "Background: Many studies on circular RNAs (circRNAs) have recently been published. However, the function of circRNAs in recurrent implantation failure (RIF) is unknown and remains to be explored. This study aims to determine the regulatory mechanisms of circRNAs in RIF. Methods: Microarray data of RIF circRNA (GSE147442), microRNA (miRNA; GSE71332), and messenger RNA (mRNA; GSE103465) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNA, miRNA, and mRNA. The circRNA-miRNA-mRNA network was constructed by Cytoscape 3.8.0 software, then the protein-protein interaction (PPI) network was constructed by STRING database, and the hub genes were identified by cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in RIF. Finally, the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the hub genes were performed by clusterProfiler package of Rstudio software, and Reactome Functional Interaction (FI) plug-in was used for reactome analysis to comprehensively analyze the mechanism of hub genes in RIF. Results: A total of eight upregulated differentially expressed circRNAs (DECs), five downregulated DECs, 56 downregulated differentially expressed miRNAs (DEmiRs), 104 upregulated DEmiRs, 429 upregulated differentially expressed genes (DEGs), and 1,067 downregulated DEGs were identified regarding RIF. The miRNA response elements of 13 DECs were then predicted. Seven overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 56 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of seven miRNAs with 1,496 DEGs. The circRNA-miRNA-mRNA network and PPI network were constructed through six circRNAs, seven miRNAs, and 56 mRNAs; and four hub genes (YWHAZ, JAK2, MYH9, and RAP2C) were identified. The circRNA-miRNA-hub gene regulatory subnetwork with nine regulatory axes was formed in RIF. Functional enrichment analysis and reactome analysis showed that these four hub genes were closely related to the biological functions and pathways of RIF. Conclusion: The results of this study provide further understanding of the potential pathogenesis from the perspective of circRNA-related competitive endogenous RNA network in RIF.", "claims": [{"id": "claim-method", "statement": "Data were extracted and normalized by RStudio software, and then DECs, DEmiRs, and DEGs in the endometrium of RIF patients were obtained by limma package based on the Bioconductor package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33664765", "locator": "sections[4] \"Identification of Differentially Expressed Circular RNAs, Differentially Expressed MicroRNAs, and Differentially Expressed Messenger RNAs\" paragraph 2", "quote": "Data were extracted and normalized by RStudio software, and then DECs, DEmiRs, and DEGs in the endometrium of RIF patients were obtained by limma package based on the Bioconductor package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33664765", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33664765"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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