HDAC inhibition drives NOX5-dependent oxidative stress and sensitizes uveal melanoma cells to SOD1 inhibition
Highlights• Uveal melanomas express functional NOX5.• HDAC inhibitors (HDACi) increase NOX5 expression and ROS in uveal melanoma (UM) cells.• NOX5 silencing blocks HDACi-induced ROS elevation.• HDACi enhance histone acetylation and BRD4 recruitment to the NOX5 promoter.• Transcription factors Sp1/Sp3 and BRD4 are required for HDACi-mediated NOX5 upregulation.• HDACi-mediated enhancement of NOX5 expression and ROS production, if combined with additional sources of oxidant stress, may offer a novel therapeutic strategy for the treatment of UM.
Authors
- Becky A. Diebold
- Mariam M. Konaté (ORCID: https://orcid.org/0000-0003-1708-1348)
- Yongzhong Wu (ORCID: https://orcid.org/0000-0001-8367-3347)
- Smitha Antony (ORCID: https://orcid.org/0000-0003-0718-1126)
- James H. Doroshow (ORCID: https://orcid.org/0000-0002-4463-1790)
- Jennifer L. Meitzler (ORCID: https://orcid.org/0000-0001-9798-2124)
- Dinah S. Singer (ORCID: https://orcid.org/0000-0002-7369-3018)
- Ballachanda N. Devaiah (ORCID: https://orcid.org/0000-0003-1845-8418)
- David J. Mallick (ORCID: https://orcid.org/0000-0003-1768-8203)
- Guojian Jiang (ORCID: https://orcid.org/0000-0001-6358-3352)
- Krishnendu Roy (ORCID: https://orcid.org/0000-0003-0541-0714)
- Jiamo Lu
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2026-11-01
- DOI
- https://doi.org/10.1016/j.jbc.2026.113714
- Primary Topic
- Ocular Oncology and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00