Shujing Sun, Lianghui Guo, Huili Zhu
BackgroundOvarian cancer is a lethal malignancy with limited therapeutic options, highlighting the urgent need to identify reliable biomarkers and therapeutic targets. This study investigates the clinical and oncogenic significance of β-hydroxybutyrate dehydrogenase 1 (BDH1) as a potential therapeutic target in ovarian cancer.MethodsIntegrative genomic analyses were conducted to evaluate the oncogenic potential of BDH1 by assessing its gene amplification and expression patterns in ovarian cancer. Functional assays, including BDH1 knockdown, were performed to examine its effects on proliferation, colony formation, cell cycle, and stemness. Mechanism exploration involved assessing the Wnt/β-catenin pathway. Virtual screening was used to identify BDH1 inhibitors.ResultsBDH1 was identified as a crucial oncogene in ovarian cancer progression, characterized by frequent gene amplification and overexpression, which strongly correlated with advanced disease stage and poor patient prognosis. Functionally, BDH1 promoted tumor progression by regulating G1/S transition proteins and maintaining cancer stemness via Wnt/β-catenin signaling. BDH1 depletion suppressed malignant phenotypes, confirming its oncogenic role. BDH1 was pharmacologically targeted by centrinone, which effectively downregulated oncogenic effectors.ConclusionOur study underscores BDH1 as a multifunctional oncogenic driver in ovarian cancer. The strong association of BDH1 with aggressive disease underscores its clinical relevance as a prognostic predictor, while its functional role and pharmacological inhibition position BDH1 as a promising therapeutic target for ovarian cancer.