Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34754625", "kind": "science-record", "revision": 4, "content_hash": "sha256:88777efd848898fdaac1617fefc22b2427ec7db20339a1a17350b1ca682ac077", "created_at": "2026-11-01T17:36:26Z", "updated_at": "2026-11-01T22:05:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury.", "doi": "10.7717/peerj.12375", "pmid": "34754625", "authors": ["Peng Ke", "Lin Qian", "Yi Zhou", "Liu Feng", "Zhentao Zhang", "Chengjie Zheng", "Mengnan Chen", "Xinlei Huang", "Xiaodan Wu"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a disease with high incidence rate in kidney related surgery. Micro RNA (miRNA) and transcription factors (TFs) are widely involved in the process of renal IRI through regulation of their target genes. However, the regulatory relationships and functional roles of TFs, miRNAs and mRNAs in the progression of renal IRI are insufficiently understood. The present study aimed to clarify the underlying mechanism of regulatory relationships in renal IRI.\nMETHODS: Six gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) and differently expressed miRNAs (DEMs) were identified through RRA integrated analysis of mRNA datasets (GSE39548, GSE87025, GSE52004, GSE71647, and GSE131288) and miRNA datasets (GSE29495). miRDB and TransmiR v2.0 database were applied to predict target genes of miRNA and TFs, respectively. DEGs were applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, followed with construction of protein-protein interaction (PPI) network. Then, the TF-miRNA-mRNA network was constructed. Correlation coefficient and ROC analysis were used to verify regulatory relationship between genes and their diagnostic value in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 and in vitro, the expression of hub genes and genes from the network were observed and correlation coefficient and ROC analysis were validated.\nRESULTS: A total of 21 DEMs and 187 DEGs were identified in renal IRI group compared to control group. The results of PPI analysis showed 15 hub genes. The TF-miRNA-mRNA regulatory network was constructed and several important pathways were identified and further verified, including Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd. Four regulatory loops were identified, including Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25. The hub genes and genes in the network showed good diagnostic value in mice and human.\nCONCLUSIONS: In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI. Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd were the most important pathways, while Spp1, Fos, Timp1, Tnc, Fosl2 and Junb were the most important hub genes. Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25 might be the negative feedback loops in renal IRI.", "claims": [{"id": "claim-method", "statement": "After obtaining the DEGs of each mRNA gene expression profiles, 187 RRA DEGs were obtained by RRA integrated analysis, including 135 up-regulated genes and 52 down-regulated genes (File S3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34754625", "locator": "sections[15] \"Identification of DEMs and DEGs\" paragraph 2", "quote": "After obtaining the DEGs of each mRNA gene expression profiles, 187 RRA DEGs were obtained by RRA integrated analysis, including 135 up-regulated genes and 52 down-regulated genes (File S3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw measurements are available in the Supplemental Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34754625", "locator": "sections[29] \"Data Availability\" paragraph 2", "quote": "The raw measurements are available in the Supplemental Files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34754625", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI.", "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:34754625"], "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:GSE131288"], "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:GSE131288"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34754625", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.12375", "sha256": 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pca_fit"], "assets": ["source:pmid:34754625", "data:geo:GSE131288"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE131288"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:06:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16575, "completion_tokens": 2970, "cached_tokens": 0}}, "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:34754625", "type": "paper", "label": "pmid:34754625"}, {"id": "source:pmid:34754625", "type": "manuscript", "label": "PMID 34754625 full text"}, {"id": "data:geo:GSE131288", "type": "dataset", "label": "GEO GSE131288"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34754625", "type": "paper", "label": "pmid:34754625"}, {"id": "source:pmid:34754625", "type": "manuscript", "label": "PMID 34754625 full text"}, {"id": "data:geo:GSE131288", "type": "dataset", "label": "GEO GSE131288"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34754625", "type": "extraction", "used": ["source:pmid:34754625"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE131288", "type": "accession_resolution", "used": ["data:geo:GSE131288"], "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:34754625", "parent_hash": "sha256:39f21b6a4853b82b65b33bd7faf040d92f42a72982ec8f7c783b7d239be4966d", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE131288 licence not read", "asset:data:geo:GSE131288 not downloaded", "asset:data:geo:GSE134386 licence not read", "asset:data:geo:GSE134386 not downloaded", "asset:data:geo:GSE29495 licence not read", "asset:data:geo:GSE29495 not downloaded", "asset:data:geo:GSE39548 licence not read", "asset:data:geo:GSE39548 not downloaded", "asset:data:geo:GSE52004 licence not read", "asset:data:geo:GSE52004 not downloaded", "asset:data:geo:GSE71647 licence not read", "asset:data:geo:GSE71647 not downloaded", "asset:data:geo:GSE87025 licence not read", "asset:data:geo:GSE87025 not downloaded", "asset:data:geo:GSE98622 licence not read", "asset:data:geo:GSE98622 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury.", "in the network showed good diagnostic value in mice and human. CONCLUSIONS: In this study, we fo", "lue in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE", "tic value, and correlation between the genes in mice RNA-seq datasets GSE98622 and human datasets"], "order_basis": "paper_text_order:28", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 a", "eir diagnostic value through the analysis of RNA-seq data from mice and human To verify the relia", "he experimental results, another independent RNA-seq datasets, GSE98622, was used to validate the", "ion of hub genes and their diagnostic value. RNA-seq data have the characteristics of more accura"], "order_basis": "paper_text_order:1404", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["istent with their mRNA expression (File S8). Immunohistochemical staining showed that Bsnd and Ranbp3l were h", "Downloaded from The Human Protein Atlas. (B) Immunohistochemical staining showed that Bsnd and Ranbp3l were h"], "order_basis": "paper_text_order:6632", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["(D) Bsnd and Ranbp3l were up-regulated after knockdown of Cebpb in vitro. Supplementary Materials S"], "order_basis": "paper_text_order:8175", "id": "assay:4"}, {"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": ["lemental Information 1Expression profiles of microarray datasets10.7717/peerj.12375/supp-1Click here"], "order_basis": "paper_text_order:8277", "id": "assay:5"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["PCA"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}