DDX24 inhibits clear cell renal cell carcinoma progression by directly regulating AKR1B10

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies worldwide, but only a few markers have been used to diagnose ccRCC. Here, we report the critical roles of DEAD-box helicase 24 (DDX24), a member of the DEAD-box RNA helicase family, in ccRCC. The DDX24 expression level and its prognostic value were initially detected in public data and then verified in a ccRCC tissue microarray. Subsequent in vitro and in vivo experiments were conducted on representative ccRCC cell lines. RNA sequencing and experimental studies were performed to explore the underlying mechanisms, and the associations between DDX24 expression and immune characteristics were evaluated. DDX24 levels were significantly lower in ccRCC tissues and negatively correlated with advanced clinical stage and overall survival. Functional analyses showed that DDX24 overexpression inhibited ccRCC cell proliferation, migration, and invasion, while DDX24 knockdown enhanced these phenotypes. Mechanistic studies revealed that DDX24 regulated the expression of aldo-keto reductase family 1 member B10 (AKR1B10) and epithelial-mesenchymal transition (EMT)-related transcription factors. Given the low expression of DDX24, ccRCC patients may benefit more from immunotherapies. In conclusion, these findings demonstrate that DDX24 suppresses ccRCC progression through direct regulation of AKR1B10, potentially mediated by EMT-related pathways, which provides potential therapeutic targets for ccRCC.