Integrated bioinformatics analysis of core regulatory elements involved in keloid formation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34600545", "kind": "science-record", "revision": 9, "content_hash": "sha256:35ccbef28572ad1e6481fccfef5f6ebb6fb8df1caf3a9fdddc0f5fdd55af5918", "created_at": "2026-11-01T15:41:55Z", "updated_at": "2026-11-01T22:47:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated bioinformatics analysis of core regulatory elements involved in keloid formation.", "doi": "10.1186/s12920-021-01087-7", "pmid": "34600545", "authors": ["Chuying Li", "Meitong Jin", "Yinli Luo", "Zhehu Jin", "Longquan Pi"], "journal": "BMC medical genomics", "year": 2021, "abstract": "BACKGROUND: Keloid is a benign fibro-proliferative dermal tumor formed by an abnormal scarring response to injury and characterized by excessive collagen accumulation and invasive growth. The mechanism of keloid formation has not been fully elucidated, especially during abnormal scarring. Here, we investigated the regulatory genes, micro-RNAs (miRNAs) and transcription factors (TFs) that influence keloid development by comparing keloid and normal scar as well as keloid and normal skin.\nMETHODS: Gene expression profiles (GSE7890, GSE92566, GSE44270 and GSE3189) of 5 normal scar samples, 10 normal skin samples and 18 keloid samples from the Gene Expression Omnibus (GEO) database were interrogated. Differentially expressed genes (DEGs) were identified between keloid and normal skin samples as well as keloid and normal scar samples with R Project for Statistical Computing. Gene Ontology (GO) functional enrichment analysis was also performed with R software. DEG-associated protein-protein interaction (PPI) network was constructed by STRING, followed by module selection from the PPI network based on the MCODE analysis. Regulatory relationships between TF/miRNA and target genes were predicted with miRnet and cytoscape. Core regulatory genes were verified by RT-qPCR.\nRESULTS: We identified 628 DEGs, of which 626 were up-regulated and 2 were down-regulated. Seven core genes [neuropeptide Y(NPY), 5-hydroxytryptamine receptor 1A(HTR1A), somatostatin (SST), adenylate cyclase 8 (ADCY8), neuromedin U receptor 1 (NMUR1), G protein subunit gamma 3 (GNG3), and G protein subunit gamma 13 (GNG13)] all belong to MCODE1 and were enriched in the \"G protein coupled receptor signaling pathway\" of the GO biological process category. Furthermore, nine core miRNAs (hsa-mir-124, hsa-let-7, hsa-mir-155, hsa-mir-26a, hsa-mir-941, hsa-mir-10b, hsa-mir-20, hsa-mir-31 and hsa-mir-372), and two core TFs (SP1 and TERT) were identified to play important roles in keloid formation. In the TF/miRNA-target gene network, both hsa-mir-372 and hsa-mir-20 had a regulatory effect on GNG13, ADCY8 was predicted to be target by hsa-mir-10b, and HTR1A and NPY were potentially by SP1. Furthermore, the expression of core regulatory genes (GNG13, ADCY8, HTR1A and NPY) was validated in clinical samples.\nCONCLUSIONS: GNG13, ADCY8, NPY and HTR1A may act as core genes in keloid formation and these core genes establish relationship with SP1 and miRNA (hsa-mir-372, hsa-mir-20, hsa-mir-10b), which may influence multiple signaling pathways in the pathogenesis of keloid.", "claims": [{"id": "claim-method", "statement": "Screening of DEGs was then performed using the R package-limma.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34600545", "locator": "sections[4] \"Data preparation and screening for DEGs\" paragraph 2", "quote": "Screening of DEGs was then performed using the R package-limma."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE7890, GSE92566, GSE44270 and GSE3189 mRNA expression profiles (Homo sapiens) were downloaded from the Gene Expression Omnibus (GEO) database. Ten samples (five keloid and five normal scars) from GSE7890, twelve samples (nine keloid and three normal skin) from GSE44270, four keloid samples from GSE92566, and seven normal skin samples were from GSE3189.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34600545", "locator": "sections[3] \"Data resources\" paragraph 2", "quote": "GSE7890, GSE92566, GSE44270 and GSE3189 mRNA expression profiles (Homo sapiens) were downloaded from the Gene Expression Omnibus (GEO) database. Ten samples (five keloid and five normal scars) from GSE7890, twelve samples (nine keloid and three normal skin) from GSE44270, four keloid samples from GSE92566, and seven normal skin samples were from GSE3189."}], "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:34600545"], "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:GSE3189"], "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:GSE3189"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34600545", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-021-01087-7", "sha256": "sha256:bacbd67b94acebb2381bc1fa55c2f896b7153f01fb01ce5b0bd962d26c29f69b", "bytes": 32886, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12920-021-01087-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8487518", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE3189", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3189", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE3189", "version": null, "note": "GSE7890, GSE92566, GSE44270 and GSE3189 mRNA expression profiles (Homo sapiens) were downloaded from the Gene Expression Omnibus (GEO) database. 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Ten samples (five keloid and five normal scars) from GSE7890, twelve samples (nine keloid and three normal skin) from GSE44270, four keloid samples from GSE92566, and seven normal skin samples were from GSE3189.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE7890, GSE92566, GSE44270 and GSE3189 mRNA expression profiles (Homo sapiens) were downloaded from the Gene Expression Omnibus (GEO) database. 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"sha256:9982290dbbff3e9f604a87e9b2b5cab3ef977dc2e27c76bb51fda1db2f1b6165", "bytes": 1300, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab1", "version": null, "note": "The top five results of GO analysis of the common DEGs ranked by p value", "structure": {"pmcid": "PMC8487518", "section_index": 11, "section_title": "GO functional enrichment analysis", "row_count": 19, "column_count": 4}, "table": {"label": "Table 1", "caption": "The top five results of GO analysis of the common DEGs ranked by p value", "rows": [["GO/ID", "Term", "p value", "Count"], ["GO/BP", "", "", ""], ["GO:0048018", "Receptor ligand activity", "2.75303E−10", "52"], ["GO:0030546", "Signaling receptor activator activity", "4.27219E−10", "52"], ["GO:0007267", "Cell–cell signaling", "1.73456E−09", "121"], ["GO:0030545", "Receptor regulator activity", "9.92932E−09", "52"], ["GO:0099537", "Trans-synaptic signaling", "1.19345E−08", 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Core regulatory genes were verified by RT-qPCR. RESULTS: We identified 628 DEGs, of which 6", "e. Core regulatory genes were verified by RT-qPCR. 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