Targeting the dual miRNA/BMP2 network: LncRNA H19-mediated temozolomide resistance unveils novel therapeutic strategies in glioblastoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40297808", "kind": "science-record", "revision": 4, "content_hash": "sha256:d1d5b90ab3a620aee9baf7bac86a4c3ee3d73df4709072f5f776184bbded6431", "created_at": "2026-11-01T20:30:27Z", "updated_at": "2026-11-01T22:56:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Targeting the dual miRNA/BMP2 network: LncRNA H19-mediated temozolomide resistance unveils novel therapeutic strategies in glioblastoma.", "doi": "10.3389/fonc.2025.1577221", "pmid": "40297808", "authors": ["Qiudan Chen", "Shihao Zhuang", "Shuying Chen", "Biying Wu", "Qingyu Zhou", "Weifeng Wang"], "journal": "Frontiers in oncology", "year": 2025, "abstract": "Background: Long noncoding RNA (lncRNA) is known to not only be involved in various biological processes but also to play a crucial role in chemotherapy resistance. The development of resistance in glioblastoma (GBM) poses a significant challenge in clinical settings. Nonetheless, the mechanisms through which lncRNA contributes to acquired resistance to Temozolomide (TMZ) in GBM patients remain unclear.\nMethods: We identified 265 upregulated and 396 downregulated lncRNAs associated with chemoresistance in GBM from the GEO database (GSE100736). Subsequently, we assessed the expression levels of lncRNA H19, hsa-miR-138-5p, hsa-miR-22-3p, and BMP2 mRNA through quantitative polymerase chain reaction (qPCR) in GBM cells and TMZ-resistant GBM cells. Cell viability and proliferation were evaluated using CCK-8 and cell colony formation assays, respectively. Apoptosis was determined through flow cytometry analysis. The impact of gene overexpression and knockdown on cell proliferation and apoptosis was examined via cell transfection experiments. Furthermore, we investigated the influence of lncRNA H19 on tumor development using an in vivo xenograft tumor model.\nResults: The upregulation of lncRNA H19 was observed in TMZ-resistant GBM cell lines and tissues, suggesting its involvement in acquired TMZ resistance. Silencing lncRNA H19 restored TMZ sensitivity in resistant GBM cells in vitro. Conversely, overexpression of lncRNA H19 promoted GBM cell proliferation and hindered TMZ-triggered apoptosis, facilitating the acquisition of TMZ resistance. Notably, lncRNA H19 functions as a molecular decoy for hsa-miR-138-5p and hsa-miR-22-3p, and these miRNAs can reverse the acquired TMZ resistance induced by lncRNA H19 in GBM cells. Additionally, BMP2 gene expression is crucial in the lncRNA H19-mediated pathway of acquired TMZ resistance in GBM cells. Knockdown of lncRNA H19 reinstated TMZ sensitivity in vivo, whereas BMP2 overexpression reinstated TMZ resistance.\nConclusion: LncRNA H19 enhances TMZ resistance in glioblastoma through competitive RNA targeting of BMP2.", "claims": [{"id": "claim-method", "statement": "For normally distributed data, t-tests or Analysis of Variance (ANOVA) were used to test whether differences between groups were significant. Paired two-tailed Wilcoxon signed rank test was used for non-normally distributed data. Correlations were analyzed using the two-tailed Spearman parametric correlation test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40297808", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "For normally distributed data, t-tests or Analysis of Variance (ANOVA) were used to test whether differences between groups were significant. Paired two-tailed Wilcoxon signed rank test was used for non-normally distributed data. Correlations were analyzed using the two-tailed Spearman parametric correlation test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40297808", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . 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C", "138-5p overexpression group were detected by RT-qPCR. (E) the levels of hsa-miR-22-3p in the NC g", "-22-3p overexpression group were detected by RT-qPCR. ***p<0.001, ****p<0.0001, compared with NC", "and LN229TR cells. **p<0.01, ***p<0.001. (C) qPCR detection of lncRNA H19 expression levels in"], "order_basis": "paper_text_order:798", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cell colony formation assays, respectively. Apoptosis was determined through flow cytometry analys", "sion and knockdown on cell proliferation and apoptosis was examined via cell transfection experimen", "ell proliferation and hindered TMZ-triggered apoptosis, facilitating the acquisition of TMZ resista", "ility and proliferation were evaluated using CCK-8 and cell colony formation assays, respective"], "order_basis": "paper_text_order:900", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["spectively. Apoptosis was determined through flow cytometry analysis. The impact of gene overexpression", "mM, this process lasted about 6 months (36). Flow cytometry analysis of apoptosis Apoptosis assays of GB", "eatments. Finally, cells were analyzed using flow cytometry (BD FACSCanto II). Statistical analysis Stat"], "order_basis": "paper_text_order:987", "id": "assay:3"}, {"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": ["feration and apoptosis was examined via cell transfection experiments. Furthermore, we investigated th", "lysis. The impact of gene overexpression and knockdown on cell proliferation and apoptosis was exam", "way of acquired TMZ resistance in GBM cells. Knockdown of lncRNA H19 reinstated TMZ sensitivity in", "1 (A) Expression levels of lncRNA H19 after transfection with shRNA H19 in U87 cells and U87TR cells."], "order_basis": "paper_text_order:1050", "id": "assay:4"}, {"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": ["of lncRNA H19 on tumor development using an in vivo xenograft tumor model. Results: The upregula", "own of lncRNA H19 reinstated TMZ sensitivity in vivo, whereas BMP2 overexpression reinstated TMZ", "ion between H19 and hsa-miR-138-5p levels in mouse tumor tissues. (J) Correlation between H19 a", "tion between H19 and hsa-miR-22-3p levels in mouse tumor tissues. (K) Correlation between H19 a"], "order_basis": "paper_text_order:1232", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cal Culture Collection (ATCC). U87 and LN229 cell lines were cultured in Dulbecco’s modified Eagle medium suppleme", "ection (ATCC). 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