RAB40C regulates SNX9 stability

Introduction: Aim of the study was to investigate the roles and interaction mechanisms of RAB40C and SNX9 in prostate adenocarcinoma (PRAD) progression and their impact on the Hippo signaling pathway. PRAD is a significant health concern, and understanding the molecular underpinnings is essential for its effective management. Objective of this study was to identify key genes and pathways involved in PRAD using weighted gene co-expression network analysis (WGCNA) and determine the functional implications of RAB40C and its relationship with SNX9. Material and methods: WGCNA was used to chart gene co-expression patterns in PRAD. Functional enrichment analyses of significant modules were performed, and prognostic insights were derived through differential gene expression analysis. The interaction between RAB40C and SNX9 was elucidated using various in vitro assays and databases. Results: WGCNA identified a module (MEblue) highly correlated with PRAD. The hub gene was revealed, with RAB40C being central to PRAD progression. The knockdown of RAB40C inhibited PRAD cell proliferation, migration, and invasion. SNX9 was identified as a substrate protein interacting with RAB40C. The silencing of RAB40C led to increased SNX9 expression, suggesting an inverse regulatory relationship. RAB40C promoted SNX9 degradation via the ubiquitin-proteasome pathway. Silencing RAB40C reduced PRAD cell proliferation, migration, and invasion, effects that were counteracted by simultaneous SNX9 suppression. The interaction between RAB40C and SNX9 influenced target proteins of the Hippo signaling pathway. Conclusions: RAB40C is essential for the progression of PRAD, partly through modulating SNX9 levels and the Hippo signaling pathway. This interplay offers novel insights for PRAD therapeutic strategies.