Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34801043", "kind": "science-record", "revision": 4, "content_hash": "sha256:acfa8094eb6756b2768f28ddf3682e2131200d878a5d3bb365f541af2ce5a7cb", "created_at": "2026-11-01T17:36:30Z", "updated_at": "2026-11-01T22:05:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer.", "doi": "10.1186/s12935-021-02278-z", "pmid": "34801043", "authors": ["Jia Yang", "Ran Hao", "Yunlong Zhang", "Haibin Deng", "Wenjing Teng", "Zhongqi Wang"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear.\nMETHODS: Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein-protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan-Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database.\nRESULTS: In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues.\nCONCLUSION: We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic value of the 12 target genes in NSCLC patients with clinical features (Additional file 9: Fig. S9).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34801043", "locator": "sections[19] \"Prognostic analysis of target genes\" paragraph 2", "quote": "Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic value of the 12 target genes in NSCLC patients with clinical features (Additional file 9: Fig. S9)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in GEO (http:// www.ncbi.nlm.nih.gov/geo) and GDC API (https://portal.gdc.cancer.gov/) website.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34801043", "locator": "sections[29] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in GEO (http:// www.ncbi.nlm.nih.gov/geo) and GDC API (https://portal.gdc.cancer.gov/) website."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34801043", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram.", "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:34801043"], "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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