DNA damage-mediated FTO downregulation promotes CRPC progression by inhibiting FOXO3a via an m⁶A-dependent mechanism.

ABSTRACT: Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) represent a promising novel treatment for castration-resistant prostate cancer (CRPC) with encouraging results. However, the combination targets in CRPC remain largely unexplored. N6-methyladenosine (m⁶A) has been shown to play a crucial role in cancer progression and DNA damage response. Here, we observed a higher overall level of m⁶A and a downregulation of Fat mass and obesity-associated protein (FTO), which correlated with unfavorable clinicopathological parameters in prostate cancer (PCa). Functionally, reduced FTO promotes PCa growth, while overexpression of FTO has the opposite effect. Mechanistically, FOXO3a was identified as the downstream target of FTO in PCa. FTO downregulates the expression of

SUBMITTER: Xu L 

PROVIDER: S-EPMC11375469 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature