NCAPH Promotes the Proliferation of Prostate Cancer Cells Via Modulating the E2F1 Mediated PI3K/AKT/mTOR Axis

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 <i>NCAPH</i> 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 <i>E2F1</i> transcription by binding to the proximal promoter of <i>E2F1</i>, subsequently stimulating the PI3K/AKT/mTOR pathway and activating downstream targets for cell cycle progression in PCa cells. Notably, combining <i>NCAPH</i> knockdown with an mTOR inhibitor (Everolimus) or a cyclin-dependent kinase inhibitor (Flavopiridol) demonstrated promising anti-tumor effects both <i>in vitro</i> and <i>in vivo</i>. This study highlights the significant pro-tumor role of NCAPH in PCa and suggests its potential as a therapeutic target.