Construction and Bioinformatics Analysis of ceRNA Regulatory Networks in Idiopathic Pulmonary Fibrosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38871957", "kind": "science-record", "revision": 3, "content_hash": "sha256:023ebaeb3ddd2acc87288d494ff76886c09737718bf4d83a1f67ba913a1d15d1", "created_at": "2026-11-01T20:28:55Z", "updated_at": "2026-11-01T22:12:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and Bioinformatics Analysis of ceRNA Regulatory Networks in Idiopathic Pulmonary Fibrosis.", "doi": "10.1007/s10528-024-10853-y", "pmid": "38871957", "authors": ["Menglin Zhang", "Xiao Wu", "Honglan Zhu", "Chenkun Fu", "Wenting Yang", "Xiaoting Jing", "Wenqu Liu", "Yiju Cheng"], "journal": "Biochemical genetics", "year": 2025, "abstract": "Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of pulmonary fibrosis of unknown etiology. Despite ongoing research, there is currently no cure for this disease. Recent studies have highlighted the significance of competitive endogenous RNA (ceRNA) regulatory networks in IPF development. Therefore, this study investigated the ceRNA network associated with IPF pathogenesis. We obtained gene expression datasets (GSE32538, GSE32537, GSE47460, and GSE24206) from the Gene Expression Omnibus (GEO) database and analyzed them using bioinformatics tools to identify differentially expressed messenger RNAs (DEmRNAs), microRNAs (DEmiRNAs), and long non-coding RNAs (DElncRNA). For DEmRNAs, we conducted an enrichment analysis, constructed protein-protein interaction networks, and identified hub genes. Additionally, we predicted the target genes of differentially expressed mRNAs and their interacting long non-coding RNAs using various databases. Subsequently, we screened RNA molecules with ceRNA regulatory relations in the lncACTdb database based on the screening results. Furthermore, we performed disease and functional enrichment analyses and pathway prediction for miRNAs in the ceRNA network. We also validated the expression levels of candidate DEmRNAs through quantitative real-time reverse transcriptase polymerase chain reaction and analyzed the correlation between the expression of these candidate DEmRNAs and the percent predicted pre-bronchodilator forced vital capacity [%predicted FVC (pre-bd)]. We found that three ceRNA regulatory axes, specifically KCNQ1OT1/XIST/NEAT1-miR-20a-5p-ITGB8, XIST-miR-146b-5p/miR-31-5p- MMP16, and NEAT1-miR-31-5p-MMP16, have the potential to significantly affect IPF progression. Further examination of the underlying regulatory mechanisms within this network enhances our understanding of IPF pathogenesis and may aid in the identification of diagnostic biomarkers and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The GEO2R tool, available at http://www.ncbi.nlm.nih.gov/geo/geo2r, was used to identify DEGs between patients with IPF and healthy control tissues. |log fold change|> 1 and adjusted P-value < 0.05 were considered statistically significant. The 2−ΔΔCt method was employed to determine the relative expression levels of the relevant genes. The obtained data are presented as mean ± standard error of the mean and analyzed using GraphPad PRISM 9.5.0 software (USA). Differences between the two groups were determined using a t-test. p < 0.05 was regarded as statistically significant. Correlation among the candidate DEmRNAs was evaluated using Pearson's correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38871957", "locator": "sections[4] \"Differentially Expressed Genes (DEG) Identification\" paragraph 2", "quote": "The GEO2R tool, available at http://www.ncbi.nlm.nih.gov/geo/geo2r, was used to identify DEGs between patients with IPF and healthy control tissues. |log fold change|> 1 and adjusted P-value < 0.05 were considered statistically significant."}, {"asset": "source:pmid:38871957", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "The 2−ΔΔCt method was employed to determine the relative expression levels of the relevant genes."}, {"asset": "source:pmid:38871957", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "The obtained data are presented as mean ± standard error of the mean and analyzed using GraphPad PRISM 9.5.0 software (USA)."}, {"asset": "source:pmid:38871957", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "Differences between the two groups were determined using a t-test. p < 0.05 was regarded as statistically significant."}, {"asset": "source:pmid:38871957", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "Correlation among the candidate DEmRNAs was evaluated using Pearson's correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The row data included in this study are available in GEO [https://www.ncbi.nlm.nih.gov/geo/, (accessed on 25 May 2022)].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38871957", "locator": "sections[27] \"notes\" paragraph 1", "quote": "The row data included in this study are available in GEO [https://www.ncbi.nlm.nih.gov/geo/, (accessed on 25 May 2022)]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study found three ceRNA regulatory axes that may significantly affect IPF progression: KCNQ1OT1/XIST/NEAT1-miR-20a-5p-ITGB8, XIST-miR-146b-5p/miR-31-5p-MMP16, and NEAT1-miR-31-5p-MMP16.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38871957", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We found that three ceRNA regulatory axes, specifically KCNQ1OT1/XIST/NEAT1-miR-20a-5p-ITGB8, XIST-miR-146b-5p/miR-31-5p- MMP16, and NEAT1-miR-31-5p-MMP16, have the potential to significantly affect IPF progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study found three ceRNA regulatory axes that may significantly affect IPF progression: KCNQ1OT1/XIST/NEAT1-miR-20a-5p-ITGB8, XIST-miR-146b-5p/miR-31-5p-MMP16, and NEAT1-miR-31-5p-MMP16.", "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:38871957"], "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:GSE24206"], "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": {"p_value": "old change and adjusted P-value thresholds, followed by"}, "inputs": ["data:geo:GSE24206"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38871957", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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"2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE24206 not downloaded", "asset:data:geo:GSE24206 licence not read", "asset:data:geo:GSE32537 not downloaded", "asset:data:geo:GSE32537 licence not read", "asset:data:geo:GSE32538 not downloaded", "asset:data:geo:GSE32538 licence not read", "asset:data:geo:GSE47460 not downloaded", "asset:data:geo:GSE47460 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "old change and adjusted P-value thresholds, followed by"}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "reordered", "quote": "The GEO2R tool, available at http://www.ncbi.nlm.nih.gov/geo/geo2r, was used to identify DEGs between patients with IPF and healthy control tissues. |log fold change|> 1 and adjusted P-value < 0.05 were considered statistically significant. The 2−ΔΔCt method was employed to determine the relative expression levels of the relevant genes. The obtained data are presented as mean ± standard error of the mean and analyzed using GraphPad PRISM 9.5.0 software (USA). Differences between the two groups were determined using a t-test. p < 0.05 was regarded as statistically significant. Correlation among the candidate DEmRNAs was evaluated using Pearson's correlation analysis."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE32537", "GSE47460", "GSE32538", "GSE24206"], "resolved_accessions": ["GSE32537", "GSE47460", "GSE32538", "GSE24206"], "statements": ["The row data included in this study are available in GEO [https://www.ncbi.nlm.nih.gov/geo/, (accessed on 25 May 2022)]."], "basis": "The paper names GSE32537, GSE47460, GSE32538, GSE24206 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": ["pearson_r"], "assets": ["source:pmid:38871957", "data:geo:GSE24206"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE24206"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:20:56Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11065, "completion_tokens": 1716, "cached_tokens": 256}}, "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:38871957", "type": "paper", "label": "pmid:38871957"}, {"id": "source:pmid:38871957", "type": "manuscript", "label": "PMID 38871957 full text"}, {"id": "data:geo:GSE24206", "type": "dataset", "label": "GEO GSE24206"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38871957", "type": "paper", "label": "pmid:38871957"}, {"id": "source:pmid:38871957", "type": "manuscript", "label": "PMID 38871957 full text"}, {"id": "data:geo:GSE24206", "type": "dataset", "label": "GEO GSE24206"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38871957", "type": "extraction", "used": ["source:pmid:38871957"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE24206", "type": "accession_resolution", "used": ["data:geo:GSE24206"], "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:38871957", "parent_hash": "sha256:290dbf771faa6df450683c0d71c9263dfd1d997ca8c49e8ca3d0cf85468d1cb5", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE24206 licence not read", "asset:data:geo:GSE24206 not downloaded", "asset:data:geo:GSE32537 licence not read", "asset:data:geo:GSE32537 not downloaded", "asset:data:geo:GSE32538 licence not read", "asset:data:geo:GSE32538 not downloaded", "asset:data:geo:GSE47460 licence not read", "asset:data:geo:GSE47460 not downloaded", "execution.not_run", "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": ["was set at 0.01. Animal Model Male C57BL/6J mice were procured from SiPeiFu Biotechnology (http://", "lowing a one-week acclimatization period, 12 mice were randomly assigned to two groups using a rand", "in (BLM) groups. On the day of modeling, all mice were intraperitoneally injected with pentobarbita", "human type II alveolar epithelial (A549) and mouse embryonic fibroblast (3T3) cell lines were o"], "order_basis": "paper_text_order:2785", "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": 0.99, "evidence": ["manufacturer’s instructions. A549 cells were cultured in Ham’s F-12 K medium (Gibco, Thermo Fisher Sc", "her Scientific, USA), whereas 3T3 cells were cultured in Dulbecco’s Modified Eagle’s medium (Gibco, T", "lture The human type II alveolar epithelial (A549) and mouse embryonic fibroblast (3T3) cell l", "ccording to the manufacturer’s instructions. A549 cells were cultured in Ham’s F-12 K medium ("], "order_basis": "paper_text_order:3850", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["nriched in 10 MF, including inflammation and apoptosis (Fig. 7b). KEGG pathway analysis further rev"], "order_basis": "paper_text_order:5508", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The GEO2R tool, available at http://www.ncbi.nlm.nih.gov/geo/geo2r, was used to identify DEGs between patients with IPF and healthy control tissues. |log fold change|> 1 and adjusted P-value < 0.05 were considered statistically significant. The 2−ΔΔCt method was employed to determine the relative expression levels of the relevant genes. The obtained data are presented as mean ± standard error of the mean and analyzed using GraphPad PRISM 9.5.0 software (USA). Differences between the two groups were determined using a t-test. p < 0.05 was regarded as statistically significant. Correlation among the candidate DEmRNAs was evaluated using Pearson's correlation analysis."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}