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pmid:31502424
Analysis of miRNA-mRNA regulatory network revealed key genes induced by aflatoxin B1 exposure in primary human hepatocytes.
Ziyang Zhang · Dongyang Tang · Bin Wang · Zhiwei Wang · Mingjiu Liu
Molecular genetics & genomic medicine · 2019 doi:10.1002/mgg3.971
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Experiment
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Complete file
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However, comprehensive microRNA (miRNA)-message RNA (mRNA) regulatory network regarding AFB1-associated HCC is still lacking. This work was aimed to identify miRNA-mRNA network in primary human hepatocytes after AFB1 exposure.\nMETHODS: A miRNA expression dataset GSE71540 obtained from the gene expression omnibus (GEO) was used to identify differentially expressed miRNAs (DEMs) after AFB1 exposure using GEO2R. Target genes of these DEMs were identified using TargetScan V_7.2, miRDB, PITA, miRanda, and miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed at Database for Annotation, Visualization and Integrated Discovery (DAVID). miRNA-mRNA regulatory network was established by analyzing three enriched KEGG pathways significantly correlated with HCC onset and then visualized at CytoScape.\nRESULTS: In this work, nine upregulated and nine downregulated DEMs were identified. Functional enrichment analyses showed that these predicted target genes were significantly associated with cancer development. Analysis of three enriched pathways related to the onset of HCC identified 13 and nine target genes for upregulated DEMs and downregulated DEMs, respectively. Subsequently, the miRNA-mRNA regulatory networks were constructed.\nCONCLUSIONS: In conclusion, miRNA-mRNA regulatory network was established, which will help to understand the mechanism underlying the AFB1-induced onset of HCC.", "claims": [{"id": "claim-method", "statement": "GEO2R, an algorithm based on R language limma package, was employed to analyze differentially expressed miRNAs (DEMs) in this dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31502424", "locator": "sections[4] \"Identification of differentially expressed miRNAs\" paragraph 2", "quote": "GEO2R, an algorithm based on R language limma package, was employed to analyze differentially expressed miRNAs (DEMs) in this dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE71540, obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71540), is a miRNA expression profile dataset submitted by Linda Rieswijk.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31502424", "locator": "sections[3] \"Microarray dataset\" paragraph 2", "quote": "GSE71540, obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71540), is a miRNA expression profile dataset submitted by Linda Rieswijk."}], "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:31502424"], "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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["Biological process", "GO:0045944", "Positive regulation of transcription from RNA polymerase II promoter", "174", "5.08E‐22"], ["GO:0000122", "Negative regulation of transcription from RNA polymerase II promoter", "121", "1.66E‐13"], ["GO:0045893", "Positive regulation of transcription, DNA‐templated", "94", "1.00E‐12"], ["GO:0006366", "Transcription from RNA polymerase II promoter", "91", "1.22E‐11"], ["GO:0045892", "Negative regulation of transcription, DNA‐templated", "80", "2.79E‐08"], ["Molecular function", "GO:0005515", "Protein binding", "934", "3.94E‐29"], ["GO:0003700", "Transcription factor activity, sequence‐specific DNA binding", "142", "1.69E‐11"], ["GO:0001077", "Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence‐specific binding", "49", "6.02E‐09"], ["GO:0000978", "RNA polymerase II core promoter proximal region sequence‐specific DNA binding", "64", "8.19E‐09"], ["GO:0043565", "Sequence‐specific DNA binding", "81", "5.53E‐08"], ["Cellular component", "GO:0005654", "Nucleoplasm", "351", "1.12E‐19"], ["GO:0005737", "Cytoplasm", "563", "1.53E‐16"], ["GO:0005634", "Nucleus", "579", "1.72E‐16"], ["GO:0005829", "Cytosol", "372", "1.52E‐12"], ["GO:0016020", "Membrane", "266", "2.97E‐12"]], "row_count": 16, "column_count": 5, "numeric_cells": 45, "header_rows": 1, "locator": "section[12]/table-wrap[1]#mgg3971-tbl-0003"}}, {"id": "asset:table:pmid:31502424:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:64c18d1e77f5564fffd65ce9743e574332670b6c06de6f6fd580854b275c500f", "bytes": 1185, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#mgg3971-tbl-0004", "version": null, "note": "GO analysis of targets of the downregulated DEMs", "structure": {"pmcid": "PMC6825861", "section_index": 12, "section_title": "Functional analyses of the upregulated or downregulated 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE71540"], "resolved_accessions": ["GSE71540"], "statements": ["GSE71540, obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71540), is a miRNA expression profile dataset submitted by Linda Rieswijk."], "basis": "The paper names GSE71540 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:31502424", "data:geo:GSE71540", "asset:table:pmid:31502424:1", "asset:table:pmid:31502424:2", "asset:table:pmid:31502424:3", "asset:table:pmid:31502424:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE71540"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:16:02Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 20295, "completion_tokens": 960, "cached_tokens": 784}}, "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:31502424", "type": "paper", "label": "pmid:31502424"}, {"id": "source:pmid:31502424", "type": "manuscript", "label": "PMID 31502424 full text"}, {"id": "data:geo:GSE71540", "type": "dataset", "label": "GEO GSE71540"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31502424", "type": "paper", "label": "pmid:31502424"}, {"id": "source:pmid:31502424", "type": "manuscript", "label": "PMID 31502424 full text"}, {"id": "data:geo:GSE71540", "type": "dataset", "label": "GEO GSE71540"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31502424", "type": "extraction", "used": ["source:pmid:31502424"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE71540", "type": "accession_resolution", "used": ["data:geo:GSE71540"], "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:31502424", "parent_hash": "sha256:2a84a60f5f243e69177995c03340da0e93031bcdcc225504c390bca822688bbd", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE71540 licence not read", "asset:data:geo:GSE71540 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["GEO2R, an algorithm based on R language limma package, was employed to analyze differentially expressed miRNAs (DEMs) in this dataset."], "order_basis": "analysis_only", "id": "assay:1"}]}