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pmid:31747387
Identification of Potentially Functional CircRNA-miRNA-mRNA Regulatory Network in Gastric Carcinoma using Bioinformatics Analysis.
Guodong Yang · Yujiao Zhang · Jiyuan Yang
Medical science monitor : international medical journal of experimental and clinical research · 2019 doi:10.12659/MSM.916902
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31747387", "kind": "science-record", "revision": 7, "content_hash": "sha256:f24ee12a24b1cbb9d2aec12700fd9f420849e80017bae48d0a7d61ede4d38279", "created_at": "2026-11-01T15:40:52Z", "updated_at": "2026-11-01T22:01:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Potentially Functional CircRNA-miRNA-mRNA Regulatory Network in Gastric Carcinoma using Bioinformatics Analysis.", "doi": "10.12659/MSM.916902", "pmid": "31747387", "authors": ["Guodong Yang", "Yujiao Zhang", "Jiyuan Yang"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2019, "abstract": "BACKGROUND As all we know, gastric cancer (GC) is a highly aggressive disease. Recently, circular RNA (circRNA) was found to play a vital role in regulation of GC. Some circRNAs could regulate messenger RNA (mRNA) expression by functioning as a microRNA (miRNA) sponge. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved GC rarely has been explored and researched. MATERIAL AND METHODS All the differentially expressed circRNAs, miRNAs, and mRNA were derived from Gene Expression Omnibus (GEO) microarray data (GSE78092, GSE89143, GSE93415, and GSE54129). GC level 3 miRNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Furthermore, a circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape (version 3.6.1). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the functions and signaling pathways associated with these target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and cytoHubba. RESULTS The regulatory network consists of 3 circRNAs, 22 miRNAs, and 128 mRNAs. Only 3 miRNAs of the network were consistent with the expression of TCGA and were associated with some clinical features. The results of the functional analysis of 128 mRNAs showed that GO analysis and KEGG pathways of inclusion criteria were 49 and 24, respectively. PPI network and Cytoscape showed that the top 10 hub genes were MYC, CTGF, TGFBR2, TGFBR1, SERPINE1, KRAS, ZEB1, THBS1, CDK6, and TNS1; 4 of which were verified by GEPIA based on TCGA. Highly expressed SERPINE1 had a poor OS (over survival) and DFS (disease-free survival), and TGFBR1 expression increased along with the increase of clinical stages. CONCLUSIONS This study looked at a circRNA-miRNA-mRNA regulatory network associated with GC and explored the potential functions of mRNA in the network, then identified a new molecular marker for prediction, prognosis, and therapeutic targets for clinical patients.", "claims": [{"id": "claim-method", "statement": "The correlation between miRNA expression and clinical characteristics was tested by chi-square test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31747387", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "The correlation between miRNA expression and clinical characteristics was tested by chi-square test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Supplementary Tables 1–6 available from the corresponding author on request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31747387", "locator": "sections[18] \"Supplementary Data\" paragraph 2", "quote": "Supplementary Tables 1–6 available from the corresponding author on 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:31747387"], "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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"4", "2", "0.414"], ["G2+G3", "367", "183", "184", "", "185", "182", "", "183", "184"], ["T stage"], ["T1+2", "97", "37", "60", "0.006", "36", "61", "0.003", "56", "41", "0.405"], ["T3+4", "276", "150", "126", "", "151", "125", "", "131", "145"], ["Metastasis"], ["M0", "345", "168", "177", "0.051", "170", "175", "0.244", "174", "171", "0.683"], ["M1", "28", "199", "9", "", "17", "11", "", "13", "15"], ["Lymph node status"], ["N0", "120", "49", "71", "0.013", "51", "69", "0.042", "70", "50", "0.029"], ["N1–2", "253", "138", "115", "", "136", "117", "", "117", "136"], ["Stage"], ["I+II", "169", "81", "88", "0.438", "79", "90", "0.234", "89", "80", "0.374"], ["III+IV", "204", "106", "98", "", "108", "96", "", "98", "106"]], "row_count": 23, "column_count": 11, "numeric_cells": 130, "header_rows": 2, "locator": "section[13]/table-wrap[1]#t1-medscimonit-25-8777"}}, {"id": "asset:table:pmid:31747387:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a2f1e785a3c8e007a01b959900e07934813f598be7a758ef41177a9e071c026f", "bytes": 3548, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#t2-medscimonit-25-8777", "version": null, "note": "The results of GO enrichment analysis.", "structure": {"pmcid": "PMC6880644", "section_index": 14, "section_title": "GO and KEGG analysis of FmRNAs", "row_count": 50, "column_count": 3}, "table": {"label": "Table 2", "caption": "The results of GO enrichment analysis.", "rows": [["ID", "Description", "Gene ratio"], ["GO: 0001968", "Fibronectin binding", "4/122"], ["GO: 0005201", "Extracellular matrix structural constituent", "7/122"], ["GO: 0019888", "Protein phosphatase regulator activity", "5/122"], ["GO: 0046332", "SMAD binding", "5/122"], ["GO: 0019838", "Growth factor binding", "6/122"], ["GO: 0050431", "Transforming growth factor beta binding", "3/122"], ["GO: 0019208", "Phosphatase regulator activity", "5/122"], ["GO: 0001227", "Transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding", "7/122"], ["GO: 0001221", "Transcription cofactor binding", "3/122"], ["GO: 0004864", "Protein phosphatase inhibitor activity", "3/122"], ["GO: 0019212", "Phosphatase inhibitor activity", "3/122"], ["GO: 0072542", "Protein phosphatase activator activity", "2/122"], ["GO: 0048185", "Activin binding", "2/122"], ["GO: 0004857", "Enzyme inhibitor activity", "8/122"], ["GO: 0004674", "Protein serine/threonine kinase activity", "9/122"], ["GO: 0005024", "Transforming growth factor beta-activated receptor activity", "2/122"], ["GO: 0030169", "Low-density lipoprotein particle binding", "2/122"], ["GO: 0070888", "E-box binding", "3/122"], ["GO: 0019211", "Phosphatase activator activity", "2/122"], ["GO: 0004675", "Transmembrane receptor protein serine/threonine kinase activity", "2/122"], ["GO: 0003779", "Actin binding", "8/122"], ["GO: 0001223", "Transcription coactivator binding", "2/122"], ["GO: 0030742", "GTP-dependent protein binding", "2/122"], ["GO: 0019955", "Cytokine binding", "4/122"], ["GO: 0005518", "Collagen binding", "3/122"], ["GO: 0017022", "Myosin binding", "3/122"], ["GO: 0019903", "Protein phosphatase binding", "4/122"], ["GO: 0005520", "Insulin-like growth factor binding", "2/122"], ["GO: 0071813", "Lipoprotein particle binding", "2/122"], ["GO: 0071814", "Protein-lipid complex binding", "2/122"], ["GO: 0030332", "Cyclin binding", "2/122"], ["GO: 0035035", "Histone acetyltransferase binding", "2/122"], ["GO: 0051721", "Protein phosphatase 2A binding", "2/122"], ["GO: 0019199", "Transmembrane receptor protein kinase activity", "3/122"], ["GO: 0003713", "Transcription coactivator activity", "6/122"], ["GO: 1901682", "Sulfur compound transmembrane transporter activity", "2/122"], ["GO: 0030020", "Extracellular matrix structural constituent conferring tensile strength", "2/122"], ["GO: 0043531", "ADP binding", "2/122"], ["GO: 0001078", "Transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding", "4/122"], ["GO: 0019902", "Phosphatase binding", "4/122"], ["GO: 0000982", "Transcription factor activity, RNA polymerase II proximal promoter sequence-specific DNA binding", "7/122"], ["GO: 0019887", "l kinase regulator activity", "4/122"], ["GO: 0001228", "Transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding", "7/122"], ["GO: 0016706", "Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors", "2/122"], ["GO: 0051018", "Protein kinase A binding", "2/122"], ["GO: 0045309", "Protein phosphorylated amino acid binding", "2/122"], ["GO: 0005160", "Transforming growth factor beta receptor binding", "2/122"], ["GO: 0031625", "Ubiquitin protein ligase binding", "5/122"], ["GO: 0031490", "Chromatin DNA binding", "3/122"]], "row_count": 50, "column_count": 3, "numeric_cells": 100, "header_rows": 1, "locator": "section[14]/table-wrap[1]#t2-medscimonit-25-8777"}}, {"id": "asset:table:pmid:31747387:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:622c8a414652488a8da6c0458cf89251cfdf70732c508e8d78f3577c3754d6f1", "bytes": 1975, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[2]#t3-medscimonit-25-8777", "version": null, "note": "The results of KEGG pathway analysis.", "structure": {"pmcid": "PMC6880644", "section_index": 14, "section_title": "GO and KEGG analysis of FmRNAs", "row_count": 25, "column_count": 5}, "table": {"label": "Table 3", "caption": "The results of KEGG pathway analysis.", "rows": [["ID", "Description", "Gene ratio", "Bg ratio", "p Value"], ["hsa04218", "Cellular senescence", "10/57", "160/7466", "2.80E-07"], ["hsa04115", "p53 signaling pathway", "6/57", "72/7466", "1.60E-05"], ["hsa04910", "Insulin signaling pathway", "7/57", "137/7466", "7.39E-05"], ["hsa04933", "AGE-RAGE signaling pathway in diabetic complications", "6/57", "99/7466", "9.81E-05"], ["hsa05220", "Chronic myeloid leukemia", "5/57", "76/7466", "0.000265202"], ["hsa04068", "FoxO signaling pathway", "6/57", "132/7466", "0.000472257"], ["hsa04211", "Longevity regulating pathway", "6/57", "89/7466", "0.000552582"], ["hsa04371", "Apelin signaling pathway", "6/57", "137/7466", "0.000575675"], ["hsa05165", "Human papillomavirus infection", "9/57", "330/7466", "0.000794412"], ["hsa04390", "Hippo signaling pathway", "6/57", "154/7466", "0.001064365"], ["hsa05160", "Hepatitis C", "6/57", "155/7466", "0.001100757"], ["hsa04213", "Longevity regulating pathway - multiple species", "6/57", "62/7466", "0.00122559"], ["hsa04151", "PI3K-Akt signaling pathway", "9/57", "354/7466", "0.0013066"], ["hsa04137", "Mitophagy – animal", "4/57", "65/7466", "0.001462455"], ["hsa04520", "Adherens junction", "4/57", "72/7466", "0.002136126"], ["hsa05212", "Pancreatic cancer", "4/57", "75/7466", "0.002481334"], ["hsa05202", "Transcriptional misregulation in cancer", "6/57", "186/7466", "0.002786785"], ["hsa05219", "Bladder cancer", "3/57", "41/7466", "0.003662102"], ["hsa04350", "TGF-beta signaling pathway", "4/57", "85/7466", "0.003907022"], ["hsa05210", "Colorectal cancer", "4/57", "86/7466", "0.004074595"], ["hsa04015", "Rap1 signaling pathway", "6/57", "206/7466", "0.004611998"], ["hsa05161", "Hepatitis B", "5/57", "144/7466", "0.004659537"], ["hsa05222", "Small cell lung cancer", "4/57", "93/7466", "0.005385847"], ["hsa05163", "Human cytomegalovirus infection", "6/57", "225/7466", "0.007051458"]], "row_count": 25, "column_count": 5, "numeric_cells": 97, "header_rows": 1, "locator": "section[14]/table-wrap[2]#t3-medscimonit-25-8777"}}, {"id": "asset:table:pmid:31747387:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7d5f59dcb87fe5f66799dfc97f032e9c33f2354e770471f348f18d1ed7806c90", "bytes": 8210, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#t4-medscimonit-25-8777", "version": null, "note": "The rank of hub genes via various of situations.", "structure": {"pmcid": "PMC6880644", "section_index": 15, "section_title": "Screening of hub genes", "row_count": 87, "column_count": 13}, "table": {"label": "Table 4", "caption": "The rank of hub genes via various of situations.", "rows": [["Node name", "MCC", "DMNC", "MNC", "Degree", "EPC", "Bottle neck", "Ec centricity", "Closeness", "Radiality", "Betweenness", "Stress", "Clustering coefficient"], ["MYC", "609", "0.24794", "25", "30", "36.302", "49", "0.22965", "50.91667", "5.72361", "2930.436", "6766", "0.13563"], ["CTGF", "401", "0.37042", "13", "14", "35.37", "8", "0.18372", "40.61667", "5.33497", "676.2413", "2134", "0.31868"], ["TGFBR2", "396", "0.49882", "10", "10", "34.088", "3", "0.18372", "38.03333", "5.25253", "183.2476", "1158", "0.55556"], ["TGFBR1", "396", "0.49882", "10", "10", "33.892", "1", "0.18372", "38.03333", "5.25253", "183.2476", "1158", "0.55556"], ["SERPINE1", "370", "0.5012", "9", "11", "34.56", "8", "0.18372", "39.45", "5.34675", "868.6996", "2280", "0.38182"], ["KRAS", "322", "0.36053", "15", "17", "36.072", "16", "0.18372", "42.76667", "5.39386", "828.0731", "2704", "0.26471"], ["ZEB1", "318", "0.45368", "12", "12", "35.42", "8", "0.18372", "39.2", "5.28787", "194.055", "870", "0.4697"], ["THBS1", "259", "0.41901", "10", "11", "33.93", "6", "0.18372", "38.61667", "5.26431", "402.2999", "1202", "0.38182"], ["CDK6", "250", "0.47733", "9", "11", "33.692", "3", "0.18372", "38.26667", "5.20543", "428.6176", "1188", "0.36364"], ["TNS1", "240", "0.62199", "7", "7", "32.135", "1", "0.18372", "35.18333", "5.07588", "8.55088", "56", "0.80952"], ["COL1A1", "142", "0.32239", "11", "11", "33.115", "4", "0.1531", "34.35", "4.85212", "350.8601", "1722", "0.34545"], ["FOXO1", "134", "0.31924", "10", "10", "33.841", "4", "0.18372", "37.95", "5.24076", "203.7761", "800", "0.35556"], ["FOXO3", "131", "0.4082", "8", "11", "32.054", "2", "0.18372", "36.85", "5.09943", "398.0874", "1268", "0.25455"], ["DICER1", "121", "0.64826", "5", "6", "29.184", "2", "0.18372", "34.18333", "5.02877", "157.1734", "434", "0.66667"], ["CXCR4", "58", "0.37904", "8", "8", "32.284", "11", "0.18372", "36.86667", "5.2172", "178.6964", "600", "0.46429"], ["MUC1", "52", "0.47549", "6", "8", "30.378", "5", "0.18372", "36.43333", "5.1701", "366.1695", "864", "0.39286"], ["IGFBP5", "32", "0.36588", "7", "7", "28.18", "1", "0.1531", "32.31667", "4.82856", "193.0638", "622", "0.47619"], ["LAMC1", "28", "0.38039", "6", "6", "26.728", "1", "0.1531", "30.46667", "4.67546", "88.60129", "278", "0.53333"], ["CALU", "27", "0.56839", "4", "7", 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"23.103", "1", "0.1531", "28.15", "4.53414", "0", "0", "1"], ["COL5A2", "6", "0.2842", "4", "4", "19.627", "1", "0.13123", "24.70952", "3.9924", "5", "10", "0.5"], ["PPP2R5E", "5", "0", "1", "5", "19.69", "3", "0.1531", "30.61667", "4.69902", "302.8195", "790", "0"], ["CASP2", "5", "0.30898", "3", "4", "20.746", "2", "0.18372", "31.93333", "4.88745", "143.4932", "330", "0.33333"], ["SERPINH1", "5", "0.30898", "3", "4", "20.532", "2", "0.1531", "28.4", "4.52236", "171.9268", "490", "0.33333"], ["TXNIP", "4", "0.30898", "3", "3", "20.773", "2", "0.18372", "32.1", "4.93456", "12.23252", "76", "0.66667"], ["PRDM1", "4", "0.30898", "3", "3", "22.727", "1", "0.18372", "31.1", "4.85212", "0.68182", "4", "0.66667"], ["B2M", "4", "0.30779", "2", "4", "18.355", "7", "0.18372", "32.53333", "4.96989", "716.2094", "1514", "0.33333"], ["CTNND1", "4", "0.30779", "2", "4", "18.921", "5", "0.18372", "32.68333", "4.95811", "480.2316", "832", "0.16667"], ["APAF1", "4", "0.30898", "3", "3", "20.821", "1", "0.18372", "31.76667", "4.89922", "4.66667", "16", "0.66667"], ["SIN3B", "3", "0.30779", "2", "3", "18.56", "2", "0.18372", "32.26667", "4.95811", "154", "238", "0.33333"], ["FNBP1", "3", "0", "1", "3", "4.766", "3", "0.1531", "22.36667", "3.81574", "277.7906", "550", "0"], ["LDLR", "3", "0", "1", "3", "11.833", "5", "0.18372", "27.81667", "4.58125", "537.7906", "1026", "0"], ["FRK", "3", "0.30779", "2", "3", "7.811", "2", "0.18372", "24.4", "4.15727", "154", "298", "0.33333"], ["MYO6", "3", "0", "1", "3", "8.446", "3", "0.1531", "24.88333", "4.19261", "218.1825", "368", "0"], ["SESN2", "3", "0.30779", "2", "3", "21.783", "1", "0.18372", "32.85", "5.01699", "34.11001", "178", "0.33333"], ["RAB27A", "3", "0.30779", "2", "3", "8.435", "4", "0.18372", "24.86667", "4.20438", "326.2094", "692", "0.33333"], ["RAB34", "3", "0", "1", "3", "4.339", "3", "0.1531", "20.68333", "3.43888", "210.7381", "444", "0"], ["CLOCK", "3", "0", "1", "3", "16.66", "1", "0.1531", "28.1", "4.58125", "65.63025", 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