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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

Paper

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Experiment

complete

Data

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Analysis

complete

Execution

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title
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.
doi
10.3390/biomedicines12102236
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Bartosz Lenda
[1]
Marta Żebrowska-Nawrocka
[2]
Ewa Balcerczak
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Biomedicines
year
2024
abstract
Background/Objectives: The intrinsic molecular heterogeneity of glioblastoma (GBM) is one of the main reasons for its resistance to conventional treatment. 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.
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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.
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sections[6] "2.4. Glioma Bio Discovery Portal Molecular Subtype and Survival Analyses" paragraphs 1-3
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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.
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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.
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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.
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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.
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:39457549
parent_hash
sha256:2f334607be5ea4eb93d9e4b33575bc2c4b9a86725302c50f4b931013bb36946f
fork_of
null
gaps array · 10 items
[0]
asset:data:geo:GSE142719 licence not read
[1]
asset:data:geo:GSE142719 not downloaded
[2]
asset:data:geo:GSE146463 licence not read
[3]
asset:data:geo:GSE146463 not downloaded
[4]
asset:data:geo:GSE245800 licence not read
[5]
asset:data:geo:GSE245800 not downloaded
[6]
execution.not_run
[7]
review.human_critique
[8]
review.independent_reader
[9]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
logrank_test
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
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
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39457549", "kind": "science-record", "revision": 3, "content_hash": "sha256:b28bc1b7e5534b78094d1a5c614079420e86d084a13a25a41ced1a4e449fb03f", "created_at": "2026-11-01T20:29:43Z", "updated_at": "2026-11-01T22:13:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "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.", "doi": "10.3390/biomedicines12102236", "pmid": "39457549", "authors": ["Bartosz Lenda", "Marta Żebrowska-Nawrocka", "Ewa Balcerczak"], "journal": "Biomedicines", "year": 2024, "abstract": "Background/Objectives: The intrinsic molecular heterogeneity of glioblastoma (GBM) is one of the main reasons for its resistance to conventional treatment. 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. Glioma Bio Discovery Portal Molecular Subtype and Survival Analyses\" paragraphs 1-3", "quote": "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."}], "state": "complete"}, {"id": "claim-data-access", "statement": "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39457549", "locator": "sections[18] \"notes\" paragraph 1", "quote": "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."}], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE142719"], "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:GSE142719"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39457549", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/biomedicines12102236", "sha256": "sha256:f16aff17158a950277fb1227141675f67eed23ea03691fa2a3493408f6921720", "bytes": 32383, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/biomedicines12102236", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11504030", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE142719", "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=GSE142719", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE142719", "version": null, "note": "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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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.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4238207", "GSM4238208", "GSM4238209", "GSM4238210", "GSM4238211", "GSM4238212", "GSM4238213", "GSM4238214", "GSM4238215", "GSM4238216", "GSM4238217", "GSM4238218", "GSM4238219", "GSM4238220", "GSM4238221"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "HIF1α/HIF2α-miR210-3p network promotes glioblastoma proliferation and tumorigenesis through EGFR-PI3K/AKT signaling pathway with a positive feedback", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE146463", "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=GSE146463", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE146463", "version": null, "note": "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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