NOX4-derived oxidative DNA damage impairs thyroid differentiation through an epigenetic mechanism in BRAF-mutated radioactive iodine refractory papillary thyroid cancer cells.

ABSTRACT: Radioiodine (RAI) therapy, used for treating differentiated thyroid cancers (DTCs), hinges on the functional expression of the sodium-iodide symporter (NIS). However, up to 60% of papillary thyroid carcinomas, the most common DTC subtype, harbor BRAF^V600E mutations, which are strongly associated with reduced NIS expression, impaired RAI uptake, and poor differentiation scores. For patients with RAI-refractory, a promising therapeutic strategy is to restore RAI sensitivity by inducing tumor redifferentiation. Here, we demonstrate that NOX4-derived reactive oxygen species (ROS) contribute to NIS repression in BRAF^V600E-mutated thyroid cancer cells. Particularly, NOX4-generated oxidative DNA damage recruits DNA repair proteins, including OGG1 and MSH2/MSH6 proteins, whic

SUBMITTER: Radom M 

PROVIDER: S-EPMC12905579 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature