Genome-wide CRISPR/Cas9 screening identifies PTGR2 as a potential therapeutic target for sunitinib resistance in clear cell renal cell carcinoma.

ABSTRACT: Acquired and intrinsic resistance to sunitinib is a major obstacle to improving the therapeutic efficacy of treatment for clear cell renal cell carcinoma (ccRCC). This study aimed to identify novel therapeutic targets and the potential molecular mechanisms to overcome sunitinib resistance in ccRCC. Utilizing genome-wide CRISPR/Cas9 screening and resistant transcriptomics, we identified that prostaglandin reductase 2 (PTGR2) is a novel therapeutic target to overcome sunitinib resistance in ccRCC. The silencing of PTGR2 enhanced the cytotoxic effects of sunitinib in ccRCC cells, as measured by cell viability assays, and suppressed tumor growth in xenograft models. Mechanistically, PTGR2 physically interacts with lysine specific demethylase 6A (KDM6A) via endogenous/exogenous co-immunoprecipi

SUBMITTER: Chang W 

PROVIDER: S-EPMC12276353 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature