Abstract

Endometrial cancer (EC) is characterized by metabolic reprogramming, with cholesterol biosynthesis playing a critical role. However, the upstream transcriptional regulation of this process requires further elucidation. In this study, we identified POU2F1 as a key oncogenic transcription factor that drives cholesterol biosynthesis and tumor progression in EC. Integrative bioinformatics and clinical analyses revealed that POU2F1 is upregulated in EC and predicts poor prognosis. Mechanistically, POU2F1 directly activates DHCR24 and ELOVL2 transcription, thereby promoting DHCR24-mediated cholesterol biosynthesis and ELOVL2-associated lipid metabolic remodeling in EC. Functional assays demonstrated that POU2F1 promotes proliferation, migration, invasion, and xenograft growth in a DHCR24/ELOVL2-dependent manner. Clinically, POU2F1 expression was positively correlated with DHCR24 and ELOVL2 levels and served as an independent prognostic factor. Together, these findings establish the POU2F1-DHCR24/ELOVL2 axis as a critical driver of cholesterol-associated lipid metabolic reprogramming and cancer progression in EC, highlighting a potential therapeutic target for metabolic intervention.