IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38760850", "kind": "science-record", "revision": 5, "content_hash": "sha256:94eee8e6013226a8534c5f7c17ecc77893fceb76145f9dd1908c921badcbd17c", "created_at": "2026-11-01T19:20:43Z", "updated_at": "2026-11-01T22:54:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.", "doi": "10.1186/s40659-024-00512-2", "pmid": "38760850", "authors": ["Haiting Zhao", "Li Meng", "Peng Du", "Xinbin Liao", "Xin Mo", "Mengqi Gong", "Jiaxin Chen", "Yiwei Liao"], "journal": "Biological research", "year": 2024, "abstract": "BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood.\nRESULTS: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models.\nCONCLUSIONS: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.", "claims": [{"id": "claim-method", "statement": "“Limma” package (version 3.58.1) and “pheatmap” package (version 1.0.12) from R software (version 4.0.0) was applied to analyze and exhibit the DEMs and miRNAs exhibiting fold changes ≥ 0.4 and P-values ≤ 0.05 were chosen as significantly DEMs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38760850", "locator": "sections[4] \"Bioinformatics analysis\" paragraph 2", "quote": "“Limma” package (version 3.58.1) and “pheatmap” package (version 1.0.12) from R software (version 4.0.0) was applied to analyze and exhibit the DEMs and miRNAs exhibiting fold changes ≥ 0.4 and P-values ≤ 0.05 were chosen as significantly DEMs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Please contact the corresponding author for data requests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38760850", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "Please contact the corresponding author for data requests."}], "state": "complete"}, {"id": "claim-target-result", "statement": "miR-182-5p was significantly upregulated within IDH1-mutant glioma cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38760850", "locator": "sections[21] \"miR-182-5p is up-regulated in IDH1 -mutant glioma samples\" paragraph 2", "quote": "miR-182-5p expression was significantly upregulated within IDH1-mutant glioma cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "miR-182-5p was significantly upregulated within IDH1-mutant glioma cells.", "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:38760850"], "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:GSE119740"], "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:GSE119740"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38760850", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s40659-024-00512-2", "sha256": "sha256:f401219924b06c20c0ad044d1ba70a50deb72e69d2cebcfa31b86f1f046bea5c", "bytes": 58026, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s40659-024-00512-2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11100189", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE119740", "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=GSE119740", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE119740", "version": null, "note": "Please contact the corresponding author for data requests.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Please contact the corresponding author for data requests.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3382032", "GSM3382033", "GSM3382034", "GSM3382035", "GSM3382036"], "sample_count": 5, "group_sizes": null, "group_sizes_basis": null, "platform": "19057", "taxon": "Mus musculus", "title": "miRNA expression profile of Idh1 wild-type and mutant glioma initiating cells", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE119740 not downloaded", "asset:data:geo:GSE119740 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "“Limma” package (version 3.58.1) and “pheatmap” package (version 1.0.12) from R software (version 4.0.0) was applied to analyze and exhibit the DEMs and miRNAs exhibiting fold changes ≥ 0.4 and P-values ≤ 0.05 were chosen as significantly DEMs."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Furthermore", "posite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; a", "-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-18"], "order_basis": "paper_text_order:647", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ession. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability", "ieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-", "ibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check", "those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-18"], "order_basis": "paper_text_order:903", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["agomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-", "CDKN2C axis against R-2HG-driven oncogenesis in mice models. 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