ArticleCell death & disease2021
Histone deacetylase 6 acts upstream of DNA damage response activation to support the survival of glioblastoma cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Dual suppression of stemness and redox adaptation in glioblastoma through filaggrin upregulation by an abiraterone-based HDAC inhibitor.Journal of biomedical science · 2026Article
- Generation and Characterization of Novel Contilisant+Tubastatin a Multitarget Small Molecules Against Glioblastoma.Pharmaceutics · 2025Article
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Targeting the Kynureninase-HDAC6-Complement Axis as a Novel Therapeutic Strategy in Glioblastoma.Epigenomes · 2025Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma.Scientific reports · 2025Article
- HDAC6 inhibition through WT161 synergizes with temozolomide, induces apoptosis, reduces cell motility, and decreases β-catenin levels in glioblastoma cells.Investigational new drugs · 2025Article
- Repurposing Linezolid in Conjunction with Histone Deacetylase Inhibitor Access in the Realm of Glioblastoma Therapies.Journal of medicinal chemistry · 2025Article
- Article
- Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.Experimental hematology & oncology · 2025Article
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Effects of a novel HDAC6-selective inhibitor's radiosensitization on cancer cells.Molecular biology reports · 2024Article
- Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment.Life (Basel, Switzerland) · 2024Review
- Targeting histone deacetylase 6 (HDAC6) to enhance radiation therapy in meningiomas in a 2D and 3D in vitro study.EBioMedicine · 2024Article
- Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024Review
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- Adapt to Persist: Glioblastoma Microenvironment and Epigenetic Regulation on Cell Plasticity.Biology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
DNA repair promotes the progression and recurrence of glioblastoma (GBM). However, there remain no effective therapies for targeting the DNA damage response and repair (DDR) pathway in the clinical setting. Thus, we aimed to conduct a comprehensive analysis of DDR genes in GBM specimens to understand the molecular mechanisms underlying treatment resistance. Herein, transcriptomic analysis of 177 well-defined DDR genes was performed with normal and GBM specimens (n = 137) from The Cancer Genome Atlas and further integrated with the expression profiling of histone deacetylase 6 (HDAC6) inhibition in temozolomide (TMZ)-resistant GBM cells and patient-derived tumor cells. The effects of HDAC6 inhibition on DDR signaling were examined both in vitro and intracranial mouse models. We found that the expression of DDR genes, involved in repair pathways for DNA double-strand breaks, was upregulated in highly malignant primary and recurrent brain tumors, and their expression was related to abnormal clinical features. However, a potent HDAC6 inhibitor, MPT0B291, attenuated the expression of these genes, including RAD51 and CHEK1, and was more effective in blocking homologous recombination repair in GBM cells. Interestingly, it resulted in lower cytotoxicity in primary glial cells than other HDAC6 inhibitors. MPT0B291 reduced the growth of both TMZ-sensitive and TMZ-resistant tumor cells and prolonged survival in mouse models of GBM. We verified that HDAC6 regulated DDR genes by affecting Sp1 expression, which abolished MPT0B291-induced DNA damage. Our findings uncover a regulatory network among HDAC6, Sp1, and DDR genes for drug resistance and survival of GBM cells. Furthermore, MPT0B291 may serve as a potential lead compound for GBM therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.