Mitochondria-related core genes and TF-miRNA-hub mrDEGs network in breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33439992", "kind": "science-record", "revision": 7, "content_hash": "sha256:6a9ae20a69b328dff671a79e8999b57d1cffb49039373249661932c42a752fd7", "created_at": "2026-11-01T15:41:22Z", "updated_at": "2026-11-01T22:02:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mitochondria-related core genes and TF-miRNA-hub mrDEGs network in breast cancer.", "doi": "10.1042/BSR20203481", "pmid": "33439992", "authors": ["Li-Rong Yan", "Ang Wang", "Zhi Lv", "Yuan Yuan", "Qian Xu"], "journal": "Bioscience reports", "year": 2021, "abstract": "BACKGROUND: Mitochondria-nuclear cross-talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. The present study aimed to construct regulatory network and seek the potential biomarkers of BC diagnosis and prognosis as well as the molecular therapeutic targets from the perspective of mitochondrial dysfunction.\nMETHODS: The microarray data of mitochondria-related encoding genes in BC cell lines were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA tissue samples, intending to identify mitochondria-related differentially expressed genes (mrDEGs). We performed enrichment analysis, PPI network, hub mrDEGs and overall survival analysis and constructed transcription factor (TF)-miRNA-hub mrDEGs network.\nRESULTS: A total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated in BC cell lines and tissues. Enrichment analyses indicated that mrDEGs were associated with several cancer-related biological processes. Moreover, 9 hub mrDEGs were identified and validated in BC cell lines and tissues. Finally, 5 hub coregulated mrDEGs, 21 miRNAs and 117 TFs were used to construct TF-miRNA-hub mrDEGs network. MYC associated zinc finger protein (MAZ), heparin binding growth factor (HDGF) and Sp2 transcription factor (SP2) regulated 3 hub mrDEGs. Hsa-mir-21-5p, hsa-mir-1-3p, hsa-mir-218-5p, hsa-mir-26a-5p and hsa-mir-335-5p regulated 2 hub mrDEGs. Overall survival analysis suggested that the up-regulation of fibronectin 1 (FN1), as well as the down-regulation of discoidin domain receptor tyrosine kinase 2 (DDR2) correlated with unfavorable prognosis in BC.\nCONCLUSION: TF-miRNA-hub mrDEGs had instruction significance for the exploration of BC etiology. The hub mrDEGs such as FN1 and DDR2 were likely to regulate mitochondrial function and be novel biomarkers for BC diagnosis and prognosis as well as the therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The correlation between coregulated hub mrDEGs and the overall survival of 1402 BC cases was analyzed by using the Kaplan–Meier plotter database (www.kmplot.com) [27]. The mRNA gene chip of BC was chosen in this database. All BC patients were divided into two groups according to the median of gene expression to perform survival curve analysis. The hazard ratios with 95% confidence intervals and P values of log-rank test were calculated and displayed in the figure.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33439992", "locator": "sections[10] \"Survival analysis based on coregulated hub mrDEGs by TFs and miRNAs\" paragraph 2", "quote": "The correlation between coregulated hub mrDEGs and the overall survival of 1402 BC cases was analyzed by using the Kaplan–Meier plotter database (www.kmplot.com) [27]. The mRNA gene chip of BC was chosen in this database. All BC patients were divided into two groups according to the median of gene expression to perform survival curve analysis. The hazard ratios with 95% confidence intervals and P values of log-rank test were calculated and displayed in the figure."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the results of this manuscript are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33439992", "locator": "sections[22] \"Data Availability\" paragraph 2", "quote": "The data that support the results of this manuscript are available from the corresponding author upon reasonable request."}], "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:33439992"], "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:GSE128610"], "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": {}, "inputs": ["data:geo:GSE128610"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33439992", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1042/BSR20203481", "sha256": 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"resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33439992:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7406c312f7c1f0d2916dbc11bcbb3b14093ff1b7a6d6f8829961421262a1a023", "bytes": 945, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T1", "version": null, "note": "Validation of mrDEGs via GSE72319 and TCGA", "structure": {"pmcid": "PMC7843495", "section_index": 12, "section_title": "The identification and validation of mrDEGs in BC", "row_count": 3, "column_count": 3}, "table": {"label": "Table 1", "caption": "Validation of mrDEGs via GSE72319 and TCGA", "rows": [["mrDEGs", "Total", "Genes name"], ["up-regulated", "23", "BGN, LSR, SEMA3F, RCN3, PADI3, DEPDC7, OASL, ISG15, H2AFJ, 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1294, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T2", "version": null, "note": "GO enrichment analysis of mitochondria-related differential expressed genes", "structure": {"pmcid": "PMC7843495", "section_index": 13, "section_title": "GO function enrichment and KEGG pathway map for mrDEGs", "row_count": 6, "column_count": 4}, "table": {"label": "Table 2", "caption": "GO enrichment analysis of mitochondria-related differential expressed genes", "rows": [["Term ID", "Term description", "FDR", "Genes"], ["GO:1901166", "neural crest cell migration involved in autonomic nervous system development", "0.00015", "FN1, NRP1, SEMA3A, SEMA3F"], ["GO:0030334", "regulation of cell migration", "0.0054", "CXCL2, DDR2, DLC1, EPB41L4B, FN1, LIMCH1, MCTP1, MEF2C, MYLK, NRP1, PIK3R1, RECK, SEMA3A"], ["GO:0007166", "cell surface receptor signaling pathway", "0.006", "ARHGEF28, BGN, CELSR1, CXCL2, DDR2, EFNA3, FN1, GPC2, ISG15, MAP3K8, MARK1, MEF2C, MITF, NRP1, OASL, PIK3R1, PYGO1, RHOQ, SEMA3A, SEMA3F, SNCA, VIM, ZEB1, ZNF106"], ["GO:0030154", "cell differentiation", "0.0172", "ANK2, ARHGEF28, ASPM, BHLHE41, CCDC136, CELSR1, CPS1, DOCK11, EFNA3, FN1, GPC2, HES4, KRT81, LSR, MARK1, MECOM, MEF2C, MGST1, MITF, NAP1L2, NFIB, NRP1, PIK3R1, PYGO1, QKI, SATB1, SEMA3A, SEMA3F, VIM, ZEB1"], ["GO:0010646", "regulation of cell communication", "0.0114", "AKAP12, ANK2, ARHGEF28, ARHGEF40, ASPM, BGN, BICC1, CXCL2, DEPDC7, DLC1, DPP4, FAM132A, FGD4, FN1, GPC2, JADE1, MAP3K8, MCTP1, MDFIC, MECOM, MEF2C, NRP1, PIK3R1, PIP5K1B, RHOQ, SEMA3A, SEMA3F, SNCA, ZEB1"]], "row_count": 6, "column_count": 4, "numeric_cells": 14, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33439992:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c816a51cb32af5eaf192c2abe2eccf6b9d229b2ffa47bfd05c6c0755d99d4ddb", "bytes": 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488, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T4", "version": null, "note": "Hub mrDEGs of MCC ≥ 6", "structure": {"pmcid": "PMC7843495", "section_index": 15, "section_title": "Selection and tissue validation of hub mrDEGs", "row_count": 10, "column_count": 3}, "table": {"label": "Table 4", "caption": "Hub mrDEGs of MCC ≥ 6", "rows": [["Genes name", "MCC", "Differentially expressed"], ["FN1", "25", "Up-regulated"], ["EFNA3", "12", "Up-regulated"], ["NRP1", "12", "Down-regulated"], ["BGN", "10", "Up-regulated"], ["RHOQ", "9", "Down-regulated"], ["COL5A2", "8", "Up-regulated"], ["SEMA3A", "7", "Down-regulated"], ["DDR2", "6", "Down-regulated"], ["SEMA3F", "6", "Up-regulated"]], "row_count": 10, "column_count": 3, "numeric_cells": 9, "header_rows": 1, "locator": "section[15]/table-wrap[1]#T4"}}, {"id": "asset:table:pmid:33439992:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cd9c9ab4bb6a42f9db14912c080f4b45b7e02d655bf17c619a4f51651281da21", "bytes": 1613, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#T5", "version": null, "note": "Hub mrDEGs of coregulated by miRNAs and TFs", "structure": {"pmcid": "PMC7843495", "section_index": 18, "section_title": "Construction and validation of TF-miRNA-hub mrDEGs network analysis", "row_count": 26, "column_count": 6}, "table": {"label": "Table 5", "caption": "Hub mrDEGs of coregulated by miRNAs and TFs", "rows": [["TF", "Hub mrDEGs", "Gene counts", "miRNA", "Hub mrDEGs", "Gene counts"], ["MAZ", "EFNA3, NRP1, RHOQ", "3", "hsa-mir-218-5p", "NRP1, FN1", "2"], ["HDGF", "DDR2, EFNA3, RHOQ", "3", "hsa-mir-26a-5p", "NRP1, FN1", "2"], ["SP2", "EFNA3, NRP1, RHOQ", "3", "hsa-mir-335-5p", "NRP1, RHOQ", "2"], ["ARID4B", "FN1, NRP1", "2", "hsa-mir-1-3p", "NRP1, FN1", "2"], ["BCL11A", "EFNA3, NRP1", "2", "hsa-mir-21-5p", "DDR2, RHOQ", "2"], ["BCL11B", "EFNA3, NRP1", "2", "hsa-mir-338-3p", "NRP1", "1"], ["CREB3L1", "EFNA3, RHOQ", "2", "hsa-mir-16-5p", "NRP1", "1"], ["CTBP2", "EFNA3, NRP1", "2", "hsa-mir-148a-3p", "NRP1", "1"], ["DRAP1", "EFNA3, FN1", "2", "hsa-mir-181a-5p", "NRP1", "1"], ["GATAD2A", "EFNA3, FN1", "2", "hsa-mir-124-3p", "NRP1", "1"], ["KLF8", "EFNA3, NRP1", "2", "hsa-mir-152-3p", "NRP1", "1"], ["MBD1", "FN1, NRP1", "2", "hsa-mir-26b-5p", "FN1", "1"], ["MLLT1", "DDR2, FN1", "2", "hsa-mir-200b-3p", "FN1", "1"], ["MXD4", "NRP1, RHOQ", "2", "hsa-let-7g-5p", "FN1", "1"], ["TGIF2", "FN1, RHOQ", "2", "hsa-mir-200c-3p", "FN1", "1"], ["TSHZ1", "EFNA3, NRP1", "2", "hsa-mir-548a-3p", "DDR2", "1"], ["WT1", "EFNA3, NRP1", "2", "hsa-mir-129-2-3p", "DDR2", "1"], ["ZBTB7A", "EFNA3, RHOQ", "2", "hsa-mir-375", "RHOQ", "1"], ["ZFP2", "EFNA3, FN1", "2", "hsa-mir-210-3p", "EFNA3", "1"], ["ZNF2", "EFNA3, NRP1", "2", "hsa-mir-224-5p", "EFNA3", "1"], ["ZNF324", "EFNA3, FN1", "2", "hsa-mir-330-3p", "EFNA3", "1"], ["ZNF423", "EFNA3, NRP1", "2", "", "", ""], ["ZNF580", "FN1, NRP1", "2", "", "", ""], ["ZNF589", "DDR2, RHOQ", "2", "", "", ""], ["ZNF610", "EFNA3, NRP1", "2", "", "", ""]], "row_count": 26, "column_count": 6, "numeric_cells": 74, "header_rows": 1, "locator": "section[18]/table-wrap[1]#T5"}}], "gaps": ["asset:data:geo:GSE128610 not downloaded", "asset:data:geo:GSE128610 licence not read", "asset:data:geo:GSE72319 not downloaded", "asset:data:geo:GSE72319 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The correlation between coregulated hub mrDEGs and the overall survival of 1402 BC cases was analyzed by 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The mRNA gene chip of BC was chosen in this database. All BC patients were divided into two groups according to the median of gene expression to perform survival curve analysis. 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