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pmid:38226266

Identifying potential ferroptosis key genes for diagnosis and treatment of postmenopausal osteoporosis through competitive endogenous RNA network analysis.

Chengcheng Huang · Yang Li · Bo Li · Xiujuan Liu · Dan Luo · Yuan Liu · Mengjuan Wei · ZhenGuo Yang · Yunsheng Xu

Heliyon · 2024 doi:10.1016/j.heliyon.2023.e23672

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complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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title
Identifying potential ferroptosis key genes for diagnosis and treatment of postmenopausal osteoporosis through competitive endogenous RNA network analysis.
doi
10.1016/j.heliyon.2023.e23672
pmid
38226266
authors array · 9 items
[0]
Chengcheng Huang
[1]
Yang Li
[2]
Bo Li
[3]
Xiujuan Liu
[4]
Dan Luo
[5]
Yuan Liu
[6]
Mengjuan Wei
[7]
ZhenGuo Yang
[8]
Yunsheng Xu
journal
Heliyon
year
2024
abstract
Objective: Postmenopausal osteoporosis (PMOP) is a common systemic metabolic bone disorder that is owing to the reduced estrogen secretion and imbalance of bone absorption and bone formation in postmenopausal women. Ferroptosis has been identified as a novel modulatory mechanism of osteoporosis. Nevertheless, the particular modulatory mechanism between ferroptosis and PMOP is still unclear. The objective of the current investigation was to detect potential biomarkers connected to ferroptosis in PMOP and discover its probable mechanism through bioinformatics. Methods: We downloaded PMOP-related microarray datasets from the database of Gene Expression Omnibus (GEO) and obtained the differentially expressed genes (DEGs). Utilizing bioinformatics analysis, the DEGs were intersected with the ferroptosis dataset to obtain ferroptosis-connected mRNAs. Enrichment analysis employing KOBAS 3.0 was conducted to comprehend the biological functions and enrichment pathways of the DEGs. The generation of the protein-protein interaction (PPI) network was conducted with the aim of identifying central genes. Lastly, the coexpression and competitive endogenous RNA (ceRNA) networks were built using Cytoscape. With the help of external datasets GSE56815 to verify the reliability of the hub genes by plotting ROC curves. Results: We identified 178 DE microRNAs (miRNAs), 138 DE circular RNAs (circRNAs), and 86 ferroptosis-related mRNAs. Enrichment analysis exhibited that mRNAs were primarily connected with the signaling pathways of PI3K/Akt, metabolism, mTOR, FoxO, HIF-1, AMPK, MAPK, ferroptosis, VEGF, and NOD-like receptors. Generation of the PPI network detected eight hub genes. The circRNA/miR-23b-3p/PTEN axis may relieve PMOP by inhibiting ferroptosis through targeting the pathway of PI3K/Akt signaling, which is a vital modulatory pathway for PMOP progression. Moreover, the ROC curves ultimately indicates that the four hub genes have greater diagnostic importance in PMOP samples in contrast to the normal group samples, which may be possible markers for PMOP diagnosis. Conclusions: Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management. Moreover, the circRNA/miR-23b-3p/PTEN axis may relieve PMOP by suppressing ferroptosis through targeting the pathway of PI3K/Akt signaling, providing a new avenue to explore the pathogenesis of PMOP.
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GEO2R online program was used to conduct analysis for the raw submitter-supplied data from the microarrays and to subsequently detect differentially expressed (DE) miRNAs and DEcircRNAs in PMOP.
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The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.
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Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management.
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Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management.
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Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38226266", "kind": "science-record", "revision": 3, "content_hash": "sha256:1b91bbaac73bbb972da00d6fd2764ff1616f63add2b2bf1e56aaf8740578ef94", "created_at": "2026-11-01T19:20:08Z", "updated_at": "2026-11-01T22:11:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identifying potential ferroptosis key genes for diagnosis and treatment of postmenopausal osteoporosis through competitive endogenous RNA network analysis.", "doi": "10.1016/j.heliyon.2023.e23672", "pmid": "38226266", "authors": ["Chengcheng Huang", "Yang Li", "Bo Li", "Xiujuan Liu", "Dan Luo", "Yuan Liu", "Mengjuan Wei", "ZhenGuo Yang", "Yunsheng Xu"], "journal": "Heliyon", "year": 2024, "abstract": "Objective: Postmenopausal osteoporosis (PMOP) is a common systemic metabolic bone disorder that is owing to the reduced estrogen secretion and imbalance of bone absorption and bone formation in postmenopausal women. Ferroptosis has been identified as a novel modulatory mechanism of osteoporosis. Nevertheless, the particular modulatory mechanism between ferroptosis and PMOP is still unclear. The objective of the current investigation was to detect potential biomarkers connected to ferroptosis in PMOP and discover its probable mechanism through bioinformatics.\nMethods: We downloaded PMOP-related microarray datasets from the database of Gene Expression Omnibus (GEO) and obtained the differentially expressed genes (DEGs). Utilizing bioinformatics analysis, the DEGs were intersected with the ferroptosis dataset to obtain ferroptosis-connected mRNAs. Enrichment analysis employing KOBAS 3.0 was conducted to comprehend the biological functions and enrichment pathways of the DEGs. The generation of the protein-protein interaction (PPI) network was conducted with the aim of identifying central genes. Lastly, the coexpression and competitive endogenous RNA (ceRNA) networks were built using Cytoscape. With the help of external datasets GSE56815 to verify the reliability of the hub genes by plotting ROC curves.\nResults: We identified 178 DE microRNAs (miRNAs), 138 DE circular RNAs (circRNAs), and 86 ferroptosis-related mRNAs. Enrichment analysis exhibited that mRNAs were primarily connected with the signaling pathways of PI3K/Akt, metabolism, mTOR, FoxO, HIF-1, AMPK, MAPK, ferroptosis, VEGF, and NOD-like receptors. Generation of the PPI network detected eight hub genes. The circRNA/miR-23b-3p/PTEN axis may relieve PMOP by inhibiting ferroptosis through targeting the pathway of PI3K/Akt signaling, which is a vital modulatory pathway for PMOP progression. Moreover, the ROC curves ultimately indicates that the four hub genes have greater diagnostic importance in PMOP samples in contrast to the normal group samples, which may be possible markers for PMOP diagnosis.\nConclusions: Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management. Moreover, the circRNA/miR-23b-3p/PTEN axis may relieve PMOP by suppressing ferroptosis through targeting the pathway of PI3K/Akt signaling, providing a new avenue to explore the pathogenesis of PMOP.", "claims": [{"id": "claim-method", "statement": "GEO2R online program was used to conduct analysis for the raw submitter-supplied data from the microarrays and to subsequently detect differentially expressed (DE) miRNAs and DEcircRNAs in PMOP.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38226266", "locator": "sections[4] \"Data processing and analysis of differential expression\" paragraph 2", "quote": "GEO2R online program was used to conduct analysis for the raw submitter-supplied data from the microarrays and to subsequently detect differentially expressed (DE) miRNAs and DEcircRNAs in PMOP."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38226266", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38226266", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management.", "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:38226266"], "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:GSE161361"], "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:GSE161361"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38226266", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e23672", "sha256": "sha256:4adb7e5a506fe9defb41696229e666eeb9c62b78d0bc5efa02b6870895d94153", "bytes": 33823, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2023.e23672", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10788451", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE161361", "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=GSE161361", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE161361", "version": null, "note": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4905321", "GSM4905322", "GSM4905323", "GSM4905324", "GSM4905325", "GSM4905326"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "28148", "taxon": "Homo sapiens", "title": "Identification of exosomal circRNAs as potential biomarkers for postmenopausal osteoporosis", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE201543", "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=GSE201543", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE201543", "version": null, "note": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM6067330", "GSM6067331", "GSM6067332", "GSM6067333", "GSM6067334", "GSM6067335", "GSM6067336", "GSM6067337", "GSM6067338", "GSM6067339"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "20712", "taxon": "Homo sapiens", "title": "Bone metabolism-related serum miRNAs to diagnose postmenopausal osteoporosis in middle-aged and elderly women", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE56815", "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=GSE56815", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE56815", "version": null, "note": "The data related to our research has been stored in a publicly available repository. The GSE datasets are accessible in the database of GEO (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifier(s):GSE161361 and GSE201543.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data related to our research has been stored in a publicly available repository. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:38226266", "data:geo:GSE161361"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE161361"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:05:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9773, "completion_tokens": 1456, "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:38226266", "type": "paper", "label": "pmid:38226266"}, {"id": "source:pmid:38226266", "type": "manuscript", "label": "PMID 38226266 full text"}, {"id": "data:geo:GSE161361", "type": "dataset", "label": "GEO GSE161361"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38226266", "type": "paper", "label": "pmid:38226266"}, {"id": "source:pmid:38226266", "type": "manuscript", "label": "PMID 38226266 full text"}, {"id": "data:geo:GSE161361", "type": "dataset", "label": "GEO GSE161361"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38226266", "type": "extraction", "used": ["source:pmid:38226266"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE161361", "type": "accession_resolution", "used": ["data:geo:GSE161361"], "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:38226266", "parent_hash": "sha256:123dc5633b813a4ec42525ccbdd6b6b57e0ba127315cb86fed0d8bff3b79ca4d", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE161361 licence not read", "asset:data:geo:GSE161361 not downloaded", "asset:data:geo:GSE201543 licence not read", "asset:data:geo:GSE201543 not downloaded", "asset:data:geo:GSE56815 licence not read", "asset:data:geo:GSE56815 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": "analysis_only", "id": "assay:1"}]}