Construction of a circular RNA-microRNA-messenger RNA regulatory network of hsa_circ_0043256 in lung cancer by integrated analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34806315", "kind": "science-record", "revision": 4, "content_hash": "sha256:e26079fc978b77771cfdf51c2cce7fc3dfe772fa569061a83ad40763e3e7d3cc", "created_at": "2026-11-01T17:36:31Z", "updated_at": "2026-11-01T22:05:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of a circular RNA-microRNA-messenger RNA regulatory network of hsa_circ_0043256 in lung cancer by integrated analysis.", "doi": "10.1111/1759-7714.14226", "pmid": "34806315", "authors": ["Yongwen Li", "Ruifeng Shi", "Guangsheng Zhu", "Chen Chen", "Hua Huang", "Min Gao", "Songlin Xu", "Peijun Cao", "Zihe Zhang", "Di Wu", "Xuanguang Li", "Hongyu Liu", "Jun Chen"], "journal": "Thoracic cancer", "year": 2022, "abstract": "BACKGROUND: Patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stages and with a poor 5-year survival rate. There is a critical need to identify novel biomarkers to improve the therapy and overall prognosis of this disease.\nMETHODS: Differentially expressed genes (DEGs) were identified from three profiles of GSE101586, GSE101684 and GSE112214 using Venn diagrams. hsa_circ_0043256 were validated using quantitative real-time polymerase chain reaction (RT-qPCR). The circular RNA-microRNA-messenger RNA (circRNA-miRNA-mRNA) regulatory network was constructed with Cytoscape 3.7.0. Hub genes were identified with protein interaction (PPI) and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using a Kaplan-Meier (KM) plotter. The effects of hsa_circ_0043256 on cell proliferation and cell cycles were evaluated by EdU staining and flow cytometry, respectively.\nRESULTS: hsa_circ_0043256, hsa_circ_0029426 and hsa_circ_0049271 were obtained. Following RT-qPCR validation, hsa_circ_0043256 was selected for further analysis. In addition, functional experiment results indicated that hsa_circ_0043256 could inhibit cell proliferation and cell-cycle progression of NSCLC cells in vitro. Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated DEGs might be associated with lung cancer onset and progression. A PPI network based on the 209 genes was established, and five hub genes (BIRC5, SHCBP1, CCNA2, SKA3, and GINS1) were determined. Following verification of five hub genes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led to poor overall survival.\nCONCLUSION: Our study constructed a circRNA-miRNA-mRNA network of hsa_circ_0043256. hsa_circ_0043256 may be a potential therapeutic target for lung cancer.", "claims": [{"id": "claim-method", "statement": "Student's t‐tests were used for comparison of two sample groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34806315", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Student's t‐tests were used for comparison of two sample groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Three circRNA expression profiles (GSE101586, GSE101684 and GSE112214) were downloaded from the GEO, (www.ncbi.nlm.nih.gov/geo/), analyzed on the Agilent‐069978 Arraystar Human CircRNA microarray V1 GPL19978 platform.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34806315", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "Three circRNA expression profiles (GSE101586, GSE101684 and GSE112214) were downloaded from the GEO, (www.ncbi.nlm.nih.gov/geo/), analyzed on the Agilent‐069978 Arraystar Human CircRNA microarray V1 GPL19978 platform."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34806315", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed.", "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:34806315"], "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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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8720627", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE101586", "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=GSE101586", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE101586", "version": null, "note": "Three circRNA expression profiles (GSE101586, GSE101684 and GSE112214) were downloaded from the GEO, (www.ncbi.nlm.nih.gov/geo/), analyzed on the Agilent‐069978 Arraystar Human CircRNA microarray V1 GPL19978 platform.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Three circRNA expression profiles (GSE101586, GSE101684 and GSE112214) were downloaded from the GEO, (www.ncbi.nlm.nih.gov/geo/), analyzed on the Agilent‐069978 Arraystar Human CircRNA microarray V1 GPL19978 platform.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2706423", "GSM2706424", "GSM2706425", "GSM2706426", "GSM2706427", "GSM2706428", "GSM2706429", "GSM2706430", "GSM2706431", "GSM2706432"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "19978", "taxon": "Homo sapiens", "title": "Profiling circular RNA expression in lung cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE101586 not downloaded", "asset:data:geo:GSE101586 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"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": "PPI"}}, {"id": "method-3", "family": null, "specific": null, "label": "Student's t‐tests", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Student's t‐tests were used for comparison of two sample groups."}}], "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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The circular RNA-microRNA-messenger RNA (c", "nd hsa_circ_0049271 were obtained. Following RT-qPCR validation, hsa_circ_0043256 was selected fo", "tive real-time polymerase chain reaction (RT-qPCR). The circular RNA-microRNA-messenger RNA (c", "hsa_circ_0049271 were obtained. Following RT-qPCR validation, hsa_circ_0043256 was selected fo"], "order_basis": "paper_text_order:565", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["A), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using", "enes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led t"], "order_basis": "paper_text_order:870", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ll cycles were evaluated by EdU staining and flow cytometry, respectively. RESULTS: hsa_circ_0043256, hs"], "order_basis": "paper_text_order:1070", "id": "assay:3"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ression analysis of circRNAs The raw data of microarray datasets was preprocessed using GEO2R. The c"], "order_basis": "paper_text_order:2957", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["atabase (CSCD). 7 Cell culture and transient transfection The human lung adenocarcinoma (LUAD) cell li", "by GeneChem (GeneChem, China). For transient transfection, cells were seeded in six‐well culture plate", "were seeded in six‐well culture plates, and transfection was performed at 90% cell confluence using L"], "order_basis": "paper_text_order:3635", "id": "assay:5"}, {"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": ["e Academy of Sciences (Shanghai, China). All cell lines were cultured in RPMI 1640 medium containing 10% fetal bov", "ences (Shanghai, China). 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