Microarray-based analysis reveals a novel role of the miRNA-613/SNAI2/CXCR4 axis in atrial fibrillation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40549746", "kind": "science-record", "revision": 4, "content_hash": "sha256:ae2dc70cdc01f797caad22489fc3d74e683ff4d6c958ae6ab178492cd42fbcf9", "created_at": "2026-11-01T20:30:38Z", "updated_at": "2026-11-01T22:56:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Microarray-based analysis reveals a novel role of the miRNA-613/SNAI2/CXCR4 axis in atrial fibrillation.", "doi": "10.1371/journal.pone.0324324", "pmid": "40549746", "authors": ["Zhenyu Zhai", "Yiligong Qi", "Longlong Hu", "Zumao Gan"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUNDS: Atrial fibrillation (AF) can lead to substantial morbidity and mortality in clinic. The previous studies demonstrated that miRNAs were closely associated with several cardiovascular diseases, however, the role of miRNAs in the pathogenesis of AF has not been fully elucidated. In order to investigate the important role of miRNA in the mechanisms of AF, we conducted the study through bioinformatics analysis.\nMETHODS: We downloaded the miRNA expression profile (GSE68475) and mRNA expression profile (GSE31821) from the Gene Expression Omnibus (GEO) database to explore the differentially expressed miRNAs and mRNAs. The criteria for significant differentially expressed miRNA and mRNA using the R limma package were: adjusted P-value < 0.05, log2fold-change ≥ 1. The target mRNAs related to differentially expressed miRNAs of AF were predicted by using Functional enrichment analysis tool. We Screened overlapped mRNAs based on differentially expressed mRNAs and miRNA related mRNAs using Draw Venn Diagram. GO enrichment analysis and KEGG pathway analysis were conducted to explore the role of miRNAs and mRNAs in the pathogenesis of AF.\nRESULTS: A total of 70 differentially expressed miRNAs were screened including 33 up-regulated miRNAs and 34 downregulated miRNAs. All of 94 differentially expressed mRNAs were screened including 56 up-regulated mRNAs and 38 downregulated mRNAs. There were three co-expressed up-regulated differentially expressed genes, including CXCR4, SNAI2, and FHL1. We showed the results of GO functional enrichment analysis and KEGG pathway analysis ranked by enrichment score (-log P value) respectively.\nCONCLUSION: Compared with patients of normal sinus rhythm, miRNA-613 was significantly down-regulated in patients with AF. We demonstrated that SNAI2 and CXCR4 may target genes of miRNA-613 for the first time. Our findings may provide new ideas for clarifying the molecular mechanism of atrial fibrillation.", "claims": [{"id": "claim-method", "statement": "Differentially expressed miRNAs between AF and NSR patient samples were identified using the R limma package. Briefly, moderated t-tests were performed to compare miRNA expression between the two groups, and P values obtained from these tests were subsequently adjusted for multiple comparisons using the Benjamini-Hochberg False Discovery Rate (FDR) method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40549746", "locator": "sections[4] \"2.2. Differentially expressed miRNA identification\" paragraph 2", "quote": "Differentially expressed miRNAs between AF and NSR patient samples were identified using the R limma package. Briefly, moderated t-tests were performed to compare miRNA expression between the two groups, and P values obtained from these tests were subsequently adjusted for multiple comparisons using the Benjamini-Hochberg False Discovery Rate (FDR) method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets analyzed in this study are publicly available and can be accessed through the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Specifically, the miRNA expression profiling dataset (GSE68475) is accessible at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68475, and the mRNA expression profiling dataset (GSE31821) is available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31821.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40549746", "locator": "sections[18] \"Data Availability\" paragraph 2", "quote": "All datasets analyzed in this study are publicly available and can be accessed through the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Specifically, the miRNA expression profiling dataset (GSE68475) is accessible at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68475, and the mRNA expression profiling dataset (GSE31821) is available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31821."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Compared with patients of normal sinus rhythm, miRNA-613 was significantly down-regulated in patients with AF.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40549746", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Compared with patients of normal sinus rhythm, miRNA-613 was significantly down-regulated in patients with AF."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Compared with patients of normal sinus rhythm, miRNA-613 was significantly down-regulated in patients with AF.", "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:40549746"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31821"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"fdr_threshold": "with Benjamini-Hochberg False Discovery Rate adjustment"}, "inputs": ["data:geo:GSE31821"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40549746", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0324324", "sha256": "sha256:e298a1d9dc79206edc770b0b2c61184abdbb4bf7a5624a8d7fe51339113bb792", "bytes": 55172, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0324324", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12184911", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31821", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31821", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31821", "version": null, "note": "All datasets analyzed in this study are publicly available and can be accessed through the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). 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Role of miR-21.", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE68475", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68475", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68475", "version": null, "note": "All datasets analyzed in this study are publicly available and can be accessed through the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). 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Experimental model and c"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["es (AC16; Sigma-Aldrich, Cat# SCC-AC16) were cultured in DMEM/F-12 (Gibco, Cat# 11320−033) supplement"], "order_basis": "paper_text_order:2482", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and allowed to reach ~70% confluence before transfection. 3.4. Experimental validation of miRNA-mRNA", "FHL1 (A), SNAI2 (B) and CXCR4 (C) following transfection with hsa-miR-613 inhibitor or mimic compared"], "order_basis": "paper_text_order:3013", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ses, quantitative polymerase chain reaction (qPCR) assays were performed. Specifically, we inv", "s (FHL1, SNAI2, and CXCR4) in vitro (Fig 8). qPCR validation of miRNA-mRNA regulatory relation", "*P < 0.01; ***P < 0.001; ****P < 0.0001. The qPCR results demonstrated that the expression of", "I2 and CXCR4 expression. Collectively, these qPCR validation results provide robust experiment"], "order_basis": "paper_text_order:3258", "id": "assay:4"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differentially expressed miRNAs between AF and NSR patient samples were identified using the R limma package. Briefly, moderated t-tests were performed to compare miRNA expression between the two groups, and P values obtained from these tests were subsequently adjusted for multiple comparisons using the Benjamini-Hochberg False Discovery Rate (FDR) method."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}