Restoration of BAP1 activity via base editing suppresses anchorage-independent survival in kidney cancer.

ABSTRACT: BAP1, a deubiquitinase with a ubiquitin C-terminal hydrolase domain, functions as a tumor suppressor involved in diverse cellular processes, including DNA repair, genome stability, and apoptosis. Inactivating mutations in BAP1-particularly missense and deletion variants-are recurrent across multiple cancers, with a high prevalence in clear cell renal cell carcinoma (ccRCC), mesothelioma, and uveal melanoma. Among these, the Glu31Lys mutation in ccRCC impairs BAP1's enzymatic activity, protein stability, and DNA repair functions. Here, we investigated the physiological impact of this recurrent mutation using isogenic KMRC-20 ccRCC cell clones in which the Glu31Lys substitution was precisely corrected to wild-type glutamate via CRISPR-Cas9-mediated adenine base editing. BAP1 reactivation res

SUBMITTER: Lee D 

PROVIDER: S-EPMC12752374 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature