ArticleMolecular oncology2020
UHRF1 downmodulation enhances antitumor effects of histone deacetylase inhibitors in retinoblastoma by augmenting oxidative stress-mediated apoptosis.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Integrative multi-omics analysis unveils the connection between transcriptomic characteristics associated with mitochondria and the tumor immune microenvironment in lower-grade gliomas.Scientific reports · 2024Article
- Histone Deacetylases in Retinoblastoma.International journal of molecular sciences · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Upregulation of UHRF1 Promotes PINK1-mediated Mitophagy to Alleviates Ferroptosis in Diabetic Nephropathy.Inflammation · 2024Article
- Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma.Investigative ophthalmology & visual science · 2024Article
- Article
- Emerging New Therapeutics for Retinoblastoma.Ocular oncology and pathology · 2022Review
- Genome maintenance in retinoblastoma: Implications for therapeutic vulnerabilities.Oncology letters · 2022Review
- Curzerene suppresses progression of human glioblastoma through inhibition of glutathione S-transferase A4.CNS neuroscience & therapeutics · 2022Article
- miR-141-3p promotes retinoblastoma progressionBioengineered · 2022Article
- Targeting of histone methyltransferase DOT1L plays a dual role in chemosensitization of retinoblastoma cells and enhances the efficacy of chemotherapy.Cell death & disease · 2021Article
- Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model.Investigative ophthalmology & visual science · 2021Article
- Exploration of retinoblastoma pathogenesis with bioinformatics.Translational cancer research · 2021Article
- Chromatin regulators in retinoblastoma: Biological roles and therapeutic applications.Journal of cellular physiology · 2021Review
- Article
- The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
- Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.BMC biology · 2020Article
- Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy.Frontiers in genetics · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identification of new genetic pathways or molecular targets that sensitize cancer cells to chemotherapeutic drugs may improve the efficacy of current chemotherapy. Here, we report that downmodulation of UHRF1 (ubiquitin-like with PHD and RING finger domains 1) in retinoblastoma (RB) cells increases the sensitivity to histone deacetylase (HDAC) inhibitors, augmenting apoptotic cell death. We found that UHRF1 depletion downregulates two redox-responsive genes GSTA4 (glutathione S-transferase α4) and TXN2 (thioredoxin-2) in RB cells, and increases the basal level of intracellular oxidative stress. Antioxidant treatment significantly reduced both basal and HDAC inhibitor-induced DNA damage and apoptosis in UHRF1-depleted cells. Knockdown of GSTA4 or TXN2 sensitized RB cells to HDAC inhibitors, demonstrating that GSTA4 and TXN2 play key roles in redox homeostasis in RB cells and the susceptibility to HDAC inhibitor treatment upon UHRF1 depletion. In human primary RB, GSTA4 and TXN2 proteins were found to be mostly elevated along with high UHRF1 expression. In addition to augmentation of apoptosis in UHRF1-depleted RB cells, we also show that UHRF1 downmodulation derepresses the expression of photoreceptor-specific genes in RB cells in cooperation with a HDAC inhibitor MS-275 and promotes neuron-like differentiation. However, further investigation revealed that the enhanced growth-inhibitory effects of MS-275 in UHRF1-depleted cells were still mainly due to robust apoptosis induction rather than differentiation-mediated growth arrest. Consistent with our findings, UHRF1 depletion in RB cells increased the therapeutic efficacy of MS-275 in murine orthotopic xenografts. These results provide a novel basis for potential benefits of UHRF1 targeting for RB treatment.
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