Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39867575", "kind": "science-record", "revision": 3, "content_hash": "sha256:cc056464a609896afa2c030948c2a94c71172618880be41f951e16b784844124", "created_at": "2026-11-01T20:30:09Z", "updated_at": "2026-11-01T22:13:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments.", "doi": "10.3389/fgene.2024.1522809", "pmid": "39867575", "authors": ["Sihui Chen", "Yi Jiang", "Guoqin Xie", "Peng Wu", "Jinyu Zhu"], "journal": "Frontiers in genetics", "year": 2024, "abstract": "Background: Ferroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.\nMethods: Based on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.\nResults: This study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.\nConclusion: The study provides a theoretical basis for the treatment of osteoporosis.", "claims": [{"id": "claim-method", "statement": "For GSE35956, GSE35958 and GSE35959, student t-tests or rank sum tests are used for comparison between two groups, and FC values are obtained by the ratio of the average expression levels between the two groups (FC > 1.5 or FC < 0.67 and P < 0.05 are considered significant differences).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39867575", "locator": "sections[16] \"2.14 Statistical analysis\" paragraph 2", "quote": "For GSE35956, GSE35958 and GSE35959, student t-tests or rank sum tests are used for comparison between two groups, and FC values are obtained by the ratio of the average expression levels between the two groups (FC > 1.5 or FC < 0.67 and P < 0.05 are considered significant differences)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) repository, accession number GSE35956, GSE35958, and GSE35959.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39867575", "locator": "sections[28] \"Data availability statement\" paragraph 2", "quote": "The data presented in the study are deposited in the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) repository, accession number GSE35956, GSE35958, and GSE35959."}], "state": "complete"}, {"id": "claim-target-result", "statement": "KMT2D expression was significantly upregulated in osteoporosis samples.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39867575", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "KMT2D expression was significantly upregulated in osteoporosis samples.", "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:39867575"], "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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Then, We used Western Blot (WB) and Quantitative real-time polymerase c", "rence among the three groups (P < 0.05). (E) Western blot results were confirmed by clinical samples,", "the three groups (P < 0.05) (Figure 4D). The Western blot results showed a significant difference betw"], "order_basis": "paper_text_order:571", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["itative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a", "es. The experimental verification results of qPCR and WB indicate that KMT2D is highly express", "m primary isolation of clinical samples. (D) QPCR results validated by clinical samples. There", "ly isolated from the sample (Figure 4C). 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