Abstract
Prostate cancer (PCa) remains a major challenge in oncology, driving the need for continuous exploration and development of innovative treatment strategies. NCAPH plays a critical role in tumorigenesis and progression across multiple cancer types; however, its specific role in PCa has yet to be fully understood. This study aims to elucidate the biological functions of NCAPH in PCa. Our findings reveal that NCAPH gene expression is upregulated in PCa patients and correlates with poor prognosis. Enrichment analysis, flow cytometry, and correlation analysis demonstrate that NCAPH promotes the PI3K/AKT/mTOR pathway and facilitates cell cycle transition in PCa cells. Additionally, we identified E2F1 as a novel downstream target of NCAPH in PCa cells. Mechanistically, ChIP analysis showed that NCAPH regulates E2F1 transcription by binding to the proximal promoter of E2F1, subsequently stimulating the PI3K/AKT/mTOR pathway and activating downstream targets for cell cycle progression in PCa cells. Notably, combining NCAPH knockdown with an mTOR inhibitor (Everolimus) or a cyclin-dependent kinase inhibitor (Flavopiridol) demonstrated promising anti-tumor effects both in vitro and in vivo. This study highlights the significant pro-tumor role of NCAPH in PCa and suggests its potential as a therapeutic target.