Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35164778", "kind": "science-record", "revision": 5, "content_hash": "sha256:caa105055655b5365ca71e095fae3d2c4f035348eeb580a8330ac6b701c96fec", "created_at": "2026-11-01T17:36:55Z", "updated_at": "2026-11-01T22:05:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis.", "doi": "10.1186/s12957-022-02503-7", "pmid": "35164778", "authors": ["Yu Gong", "Yuwen Jiao", "Xiaoyang Qi", "Jinjin Fu", "Jun Qian", "Jie Zhu", "Haojun Yang", "Liming Tang"], "journal": "World journal of surgical oncology", "year": 2022, "abstract": "BACKGROUND: Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network.\nMETHODS: Microarray datasets GSE83521 and GSE93541 were obtained from the Gene Expression Omnibus (GEO). Then, we used computational biology to identify circRNAs that were differentially expressed in both GC tissue and plasma compared to normal controls; then, we detected the expression of the selected circRNAs in gastric cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We also identified circRNA-related candidate miRNAs and their target genes with online tools. Combining the predicted miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs.\nRESULTS: GO and KEGG analysis showed that the regulation of apoptotic signaling pathway and PI3K-Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by using MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed based on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network.\nCONCLUSIONS: We propose a new circRNA-miRNA-mRNA network that is associated with the pathogenesis of GC. The network may become a new molecular biomarker and could be used to develop potential therapeutic strategies for gastric cancer.", "claims": [{"id": "claim-method", "statement": "Differential expression of the circRNAs in the two datasets was analyzed by using the GEO2R online analysis tool. The absolute value of log fold change > 1.5 and p value < 0.05 were used as cut-off criteria.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35164778", "locator": "sections[4] \"Identification of DECs\" paragraph 2", "quote": "Differential expression of the circRNAs in the two datasets was analyzed by using the GEO2R online analysis tool. The absolute value of log fold change > 1.5 and p value < 0.05 were used as cut-off criteria."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35164778", "locator": "sections[22] \"Availability of data and materials\" paragraph 2", "quote": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Among them, 3 common upregulated and 0 common downregulated circRNAs were observed in the two circRNA expression profiles.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35164778", "locator": "sections[12] \"Identification of DECs\" paragraph 2", "quote": "Among them, 3 common upregulated and 0 common downregulated circRNAs were observed in the two circRNA expression profiles."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Among them, 3 common upregulated and 0 common downregulated circRNAs were observed in the two circRNA expression profiles.", "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:35164778"], "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:GSE83521"], "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:GSE83521"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35164778", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12957-022-02503-7", "sha256": "sha256:f0b529ce89ece2a53b9e394fccc09029e02c735382c56826dc91c0ae75642330", "bytes": 37185, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12957-022-02503-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8845387", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE83521", "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=GSE83521", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE83521", "version": null, "note": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2205868", "GSM2205869", "GSM2205870", "GSM2205871", "GSM2205872", "GSM2205873", "GSM2205874", "GSM2205875", "GSM2205876", "GSM2205877", "GSM2205878", "GSM2205879"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "19978", "taxon": "Homo sapiens", "title": "Circular RNA in Stage III Gastric cancer: Tumour vs. Normal mucosa tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE93541", "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=GSE93541", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE93541", "version": null, "note": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2454433", "GSM2454434", "GSM2454435", "GSM2454436", "GSM2454437", "GSM2454438"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "19978", "taxon": "Homo sapiens", "title": "CircRNA expression profiles for 6 human plasma samples derived from patients with gastric cancer", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE83521 not downloaded", "asset:data:geo:GSE83521 licence not read", "asset:data:geo:GSE93541 not downloaded", "asset:data:geo:GSE93541 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "GEO2R online analysis tool", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differential expression of the circRNAs in the two datasets was analyzed by using the GEO2R online analysis tool. The absolute value of log fold change > 1.5 and p value < 0.05 were used as cut-off criteria."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE83521", "GSE93541"], "resolved_accessions": ["GSE83521", "GSE93541"], "statements": ["We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes."], "basis": "The paper names GSE83521, GSE93541 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": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:35164778", "data:geo:GSE83521"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE83521"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:34:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11747, "completion_tokens": 1464, "cached_tokens": 128}}, "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:35164778", "type": "paper", "label": "pmid:35164778"}, {"id": "source:pmid:35164778", "type": "manuscript", "label": "PMID 35164778 full text"}, {"id": "data:geo:GSE83521", "type": "dataset", "label": "GEO GSE83521"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35164778", "type": "paper", "label": "pmid:35164778"}, {"id": "source:pmid:35164778", "type": "manuscript", "label": "PMID 35164778 full text"}, {"id": "data:geo:GSE83521", "type": "dataset", "label": "GEO GSE83521"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35164778", "type": "extraction", "used": ["source:pmid:35164778"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE83521", "type": "accession_resolution", "used": ["data:geo:GSE83521"], "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:35164778", "parent_hash": "sha256:c2a81720ff6b1c87fac868a49db25f3fffaa0f504dbfa95c068a0aca2feb1fed", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE83521 licence not read", "asset:data:geo:GSE83521 not downloaded", "asset:data:geo:GSE93541 licence not read", "asset:data:geo:GSE93541 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ucted a circRNA-miRNA-mRNA network. METHODS: Microarray datasets GSE83521 and GSE93541 were obtained", "The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained t", "Methods Microarray analysis of gene expression Two circRNA expr", "m the Agilent-069978 Arraystar Human CircRNA microarray V1 GPL19978 platform. The GSE83521 dataset c"], "order_basis": "paper_text_order:395", "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": 0.85, "evidence": ["logy, Chinese Academy of Science. All of the cell lines were maintained under the recommended culture conditions and"], "order_basis": "paper_text_order:3137", "id": "assay:2"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}