Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer.

ABSTRACT: The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcri

SUBMITTER: Ye J 

PROVIDER: S-EPMC10427640 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature