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pmid:39457549
Comprehensive Bioinformatics Analysis Reveals the Potential Role of the hsa_circ_0001081/miR-26b-5p Axis in Regulating COL15A1 and TRIB3 within Hypoxia-Induced miRNA/mRNA Networks in Glioblastoma Cells.
Bartosz Lenda · Marta Żebrowska-Nawrocka · Ewa Balcerczak
Biomedicines · 2024 doi:10.3390/biomedicines12102236
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Experiment
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Analysis
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Complete file
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Mesenchymal GBM niches are associated with hypoxic signatures and a negative influence on patients' prognosis. To date, competing endogenous RNA (ceRNA) networks have been shown to have a broad impact on the progression of various cancers. In this study, we decided to construct hypoxia-specific microRNA/ messengerRNA (miRNA/mRNA) networks with a putative circular RNA (circRNA) regulatory component using available bioinformatics tools. Methods: For ceRNA network construction, we combined publicly available data deposited in the Gene Expression Omnibus (GEO) and interaction pairs obtained from miRTarBase and circBank; a differential expression analysis of GBM cells was performed with limma and deseq2. For the gene ontology (GO) enrichment analysis, we utilized clusterProfiler; GBM molecular subtype analysis was performed in the Glioma Bio Discovery Portal (Glioma-BioDP). Results: We observed that miR-26b-5p, generally considered a tumor suppressor, was upregulated under hypoxic conditions in U-87 MG cells. Moreover, miR-26b-5p could potentially inhibit TRIB3, a gene associated with tumor proliferation. Protein-protein interaction (PPI) network and GO enrichment analyses identified a hypoxia-specific subcluster enriched in collagen-associated terms, with six genes highly expressed in the mesenchymal glioma group. This subcluster included hsa_circ_0001081/miR-26b-5p-affected COL15A1, a gene downregulated in hypoxic U-87 MG cells yet highly expressed in the mesenchymal GBM subtype. Conclusions: The interplay between miR-26b-5p, COL15A1, and TRIB3 suggests a complex regulatory mechanism that may influence the extracellular matrix composition and the mesenchymal transformation in GBM. However, the precise impact of the hsa_circ_0001081/miR-26b-5p axis on collagen-associated processes in hypoxia-induced GBM cells remains unclear and warrants further investigation.", "claims": [{"id": "claim-method", "statement": "Differences in expression levels of the examined genes between pairs of each subtype were compared by t-test; we assumed that a p < 0.05 means that the difference is statistically significant. For survival analysis, we obtained data from the TCGA-GBM cohort deposited in the GDC Data Portal (https://portal.gdc.cancer.gov/, accessed on 19 June 2024) using the TCGAbiolinks package. A Kaplan–Meier analysis and log-rank test were conducted using the survminer and survival packages. We assumed that a log-rank p < 0.05 was statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39457549", "locator": "sections[6] \"2.4. 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These data were derived from the following resources available in the public domain: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245800 [accessed on 16 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142719 [accessed on 8 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146463 [accessed on 23 June 2024]; The original data presented in the study are openly available in Zenodo at DOI 10.5281/zenodo.13770443."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:39457549"], "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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These data were derived from the following resources available in the public domain: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245800 [accessed on 16 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142719 [accessed on 8 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146463 [accessed on 23 June 2024]; The original data presented in the study are openly available in Zenodo at DOI 10.5281/zenodo.13770443.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data presented in this study are available in the Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/, [accessed on 13 August 2024], reference numbers GSE245800, GSE142719, and GSE146463. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE245800", "GSE142719", "GSE146463"], "resolved_accessions": ["GSE245800", "GSE142719", "GSE146463"], "statements": ["The data presented in this study are available in the Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/, [accessed on 13 August 2024], reference numbers GSE245800, GSE142719, and GSE146463. These data were derived from the following resources available in the public domain: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE245800 [accessed on 16 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142719 [accessed on 8 June 2024]; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146463 [accessed on 23 June 2024]; The original data presented in the study are openly available in Zenodo at DOI 10.5281/zenodo.13770443."], "basis": "The paper names GSE245800, GSE142719, GSE146463 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:39457549", "data:geo:GSE142719"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE142719"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:36:51Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9723, "completion_tokens": 3172, "cached_tokens": 256}}, "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:39457549", "type": "paper", "label": "pmid:39457549"}, {"id": "source:pmid:39457549", "type": "manuscript", "label": "PMID 39457549 full text"}, {"id": "data:geo:GSE142719", "type": "dataset", "label": "GEO GSE142719"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39457549", "type": "paper", "label": "pmid:39457549"}, {"id": "source:pmid:39457549", "type": "manuscript", "label": "PMID 39457549 full text"}, {"id": "data:geo:GSE142719", "type": "dataset", "label": "GEO GSE142719"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39457549", "type": "extraction", "used": ["source:pmid:39457549"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE142719", "type": "accession_resolution", "used": ["data:geo:GSE142719"], "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:39457549", "parent_hash": "sha256:2f334607be5ea4eb93d9e4b33575bc2c4b9a86725302c50f4b931013bb36946f", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE142719 licence not read", "asset:data:geo:GSE142719 not downloaded", "asset:data:geo:GSE146463 licence not read", "asset:data:geo:GSE146463 not downloaded", "asset:data:geo:GSE245800 licence not read", "asset:data:geo:GSE245800 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differences in expression levels of the examined genes between pairs of each subtype were compared by t-test; we assumed that a p < 0.05 means that the difference is statistically significant. For survival analysis, we obtained data from the TCGA-GBM cohort deposited in the GDC Data Portal (https://portal.gdc.cancer.gov/, accessed on 19 June 2024) using the TCGAbiolinks package. A Kaplan–Meier analysis and log-rank test were conducted using the survminer and survival packages. We assumed that a log-rank p < 0.05 was statistically significant."], "order_basis": "analysis_only", "id": "assay:1"}]}