ArticleNeuro-oncology2021
TGF-β1 modulates temozolomide resistance in glioblastoma via altered microRNA processing and elevated MGMT.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- CUDC-907 inhibits glioblastoma and enhances glioblastoma sensitivity to temozolomide by inhibiting DNA damage repair.Genes & diseases · 2026Article
- Dual suppression of stemness and redox adaptation in glioblastoma through filaggrin upregulation by an abiraterone-based HDAC inhibitor.Journal of biomedical science · 2026Article
- Research progress on glioma drug resistance: mechanism analysis and therapeutic strategies.Frontiers in pharmacology · 2026Review
- RNA-Binding Proteins: Modulators of Canonical Wnt Signaling Pathway.International journal of molecular sciences · 2025Review
- Assessing the prognostic value of long non-coding RNAs in glioblastoma patients: findings from a systematic review and meta-analysis.Cancer cell international · 2025Review
- Harnessing the role of transforming growth factor-β in glioblastoma: a focus on phytochemicals.Medical oncology (Northwood, London, England) · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- Temozolomide-Promoted MGMT Transcription Contributes to Chemoresistance by Activating the ERK Signalling Pathway in Malignant Melanoma.Journal of cellular and molecular medicine · 2025Article
- Development and validation of disulfidptosis-related genes signature for patients with glioma.Discover oncology · 2024Article
- The pathogenesis mechanism and potential clinical value of lncRNA in gliomas.Discover oncology · 2024Review
- MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma.Molecular brain · 2024Review
- Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells.Cancer gene therapy · 2024Article
- The Impact of A3AR Antagonism on the Differential Expression of Chemoresistance-Related Genes in Glioblastoma Stem-like Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Long non-coding RNANeural regeneration research · 2024Article
- Multitarget, multiagent PLGA nanoparticles for simultaneous tumor eradication and TME remodeling in a melanoma mouse model.Drug delivery and translational research · 2024Article
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer.Upsala journal of medical sciences · 2024Review
- Interplay of Sphingolipid Metabolism in Predicting Prognosis of GBM Patients: Towards Precision Immunotherapy.Journal of Cancer · 2024Article
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-β1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-β1 in temozolomide resistance has remained unknown.
methodsThe distribution of KSRP was detected by western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long noncoding RNAs (lncRNAs) between TGF-β1-treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-β1 in temozolomide resistance.
resultsOverexpression of TGF-β1 contributed to temozolomide resistance in MGMT promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-β1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-β1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized 2 lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-β1 through Smad signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to primary miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-β1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low levels of TGF-β1 or lncRNA expression benefited from temozolomide therapy.
conclusionsOur results reveal an underlying mechanism by which TGF-β1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-β inhibitor may serve as an effective therapy for glioblastomas.
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