Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer.

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GSE101124 and GSE182471 datasets were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray classification (PAM50). The circRNA-miRNA-mRNA relationship was investigated using the Cancer-Specific CircRNA, miRDB, miRTarBase, and miRWalk databases. The circRNA-miRNA-mRNA regulatory network was annotated using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. The protein-protein interaction network was constructed by the STRING database and visualized by the Cytoscape tool. Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The Disease-Free Survival and Overall Survival analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study. We identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype. We conclude that hsa_circ_0000515/miR-486-5p/SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC subgroup of BC.", "claims": [{"id": "claim-method", "statement": "Considering the importance of the hub gene in a network, we utilized the bottleneck algorithm to screen hub-genes from the PPI network.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38635539", "locator": "sections[22] \"3.6 Identification of the hub genes with bottleneck algorithm from the PPI network\" paragraph 2", "quote": "Considering the importance of the hub gene in a network, we utilized the bottleneck algorithm to screen hub-genes from the PPI network."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The circRNA expression profiles were gathered from the Gene Expression Omnibus (GEO) database with an access code of GSE101124 [12] (the dataset includes four BC cell samples, four triple negative breast cancer (TNBC) and four Luminal-A (LumA) molecular subtype tissue samples and three non-tumoruos mammary gland tissue samples) and GSE182471 [13] (the dataset includes five BC samples and five non-tumor samples).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38635539", "locator": "sections[4] \"2.1.1 circRNA expression\" paragraph 2", "quote": "The circRNA expression profiles were gathered from the Gene Expression Omnibus (GEO) database with an access code of GSE101124 [12] (the dataset includes four BC cell samples, four triple negative breast cancer (TNBC) and four Luminal-A (LumA) molecular subtype tissue samples and three non-tumoruos mammary gland tissue samples) and GSE182471 [13] (the dataset includes five BC samples and five non-tumor samples)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The bottleneck algorithm identified ten hub genes (AHNAK, CAV1, CDK1, EGR1, FGF2, FOS, KIF11, PPARG, SDC1, and TNXB) in the breast-cancer PPI network.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38635539", "locator": "sections[22] \"3.6 Identification of the hub genes with bottleneck algorithm from the PPI network\" paragraph 2", "quote": "The subnetwork with 14 nodes (10 hub genes and 4 extended genes) and 24 (14 between hub genes and 10 between extended genes) edges was determined (Fig 8B), which uncover the crucial roles of the ten genes (AHNAK, CAV1, CDK1, EGR1, FGF2, FOS, KIF11, PPARG, SDC1, and TNXB) in BC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The bottleneck algorithm identified ten hub genes (AHNAK, CAV1, CDK1, EGR1, FGF2, FOS, KIF11, PPARG, SDC1, and TNXB) in the breast-cancer PPI network.", "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:38635539"], "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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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:38635539", "data:geo:GSE101124"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE101124"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:16:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 12999, "completion_tokens": 2552, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:38635539", "type": "paper", "label": "pmid:38635539"}, {"id": "source:pmid:38635539", "type": "manuscript", "label": "PMID 38635539 full text"}, {"id": "data:geo:GSE101124", "type": "dataset", "label": "GEO GSE101124"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38635539", "type": "paper", "label": "pmid:38635539"}, {"id": "source:pmid:38635539", "type": "manuscript", "label": "PMID 38635539 full text"}, {"id": "data:geo:GSE101124", "type": "dataset", "label": "GEO GSE101124"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38635539", "type": "extraction", "used": ["source:pmid:38635539"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE101124", "type": "accession_resolution", "used": ["data:geo:GSE101124"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:38635539", "parent_hash": "sha256:466b751607417e86249ba27994a1c63e4ea6727d1e797a6f2742b70511796e3f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE101124 licence not read", "asset:data:geo:GSE101124 not downloaded", "asset:data:geo:GSE182471 licence not read", "asset:data:geo:GSE182471 not downloaded", "asset:data:geo:GSE25066 licence not read", "asset:data:geo:GSE25066 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["genes considering the Prediction Analysis of Microarray classification (PAM50). The circRNA-miRNA-mR"], "order_basis": "paper_text_order:607", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}