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, w

SUBMITTER: Crane H 

PROVIDER: S-EPMC12496221 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature