Crane, H., Carr, I. orcid.org/0000-0001-9544-1068, Hunter, K.D. et al. (1 more author) (2025) Senataxin regulates cisplatin resistance through an R-loop-mediated mechanism in HPV-associated head and neck cancer. iScience, 28 (9). 113348. ISSN: 2589-0042
Abstract
Resistance to cisplatin is a key clinical concern in HPV-independent (HPV−) and HPV-associated (HPV+) head and neck cancer. Upregulation of DNA repair is known to contribute to cisplatin resistance and a major source of endogenous DNA damage are DNA/RNA hybrids, known as R-loops. Following creation of HPV+ and HPV− cisplatin resistant cell lines, RNA-sequencing revealed alterations in the expression of known R-loop regulators. Resistant cells had elevated global R-loop levels and in HPV+ resistant cells there was a corresponding upregulation of the R-loop resolving protein, senataxin. Depletion of senataxin led to increased sensitivity to cisplatin, an increase in DNA damage and elevated R-loops at specific genomic loci. In summary, using an in vitro model of cisplatin resistance, we identified that senataxin modulates sensitivity to cisplatin through an R-loop-mediated mechanism in HPV+ cells. R-loops may represent a potential therapeutic target and warrant further investigation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access [item type, e.g. article, conference paper, book chapter] under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Date Deposited: | 30 Sep 2025 11:26 |
Last Modified: | 30 Sep 2025 11:26 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.isci.2025.113348 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:232284 |