Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.

ABSTRACT: External beam radiotherapy (RT) is a leading first-line therapy for prostate cancer (PCa), and, in recent years, significant advances have been accomplished. However, RT resistance can arise and result in long-term recurrence or disease progression in the worst-case scenario. Thus, making crucial the discovery of new targets for PCa radiosensitization. Herein, we generated a radioresistant PCa cell line, and found p53 to be highly expressed in radioresistant PCa cells, as well as in PCa patients with recurrent/disease progression submitted to RT. Mechanism dissection revealed that RT could promote p53 expression via epigenetic modulation. Specifically, a decrease of H3K27me3 occupancy at TP53 gene promoter, due to increased KDM6B activity, was observed in radioresistant PCa cells. Furtherm

SUBMITTER: Macedo-Silva C 

PROVIDER: S-EPMC10577134 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature