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Senataxin regulates cisplatin resistance through an R-loop mediated mechanism in HPV-associated Head and Neck Cancer

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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279046 | GEO | 2025/07/29

REPOSITORIES: GEO

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Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination

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Senataxin regulates cisplatin resistance through an R-loop mediated mechanism in HPV-associated Head and Neck Cancer

Project description:Senataxin regulates cisplatin resistance through an R-loop mediated mechanism in HPV-associated Head and Neck Cancer

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