DHCR24 promotes endometrial carcinoma progression and is associated with cellular senescence regulation.

Endometrial carcinoma (EC) is a common gynecological malignancy with an increasing incidence, particularly among younger and obese women. Although early-stage EC generally has favorable outcomes, advanced and recurrent disease remains difficult to treat, highlighting the need for reliable biomarkers and biologically relevant therapeutic targets. DHCR24, a terminal enzyme in cholesterol biosynthesis, has been implicated in tumor progression, but its clinical relevance and biological role in EC remain incompletely defined. In this study, we evaluated DHCR24 expression, prognostic significance, and functional relevance in EC using public transcriptomic datasets, independent clinical specimens, in vitro assays, and an in vivo xenograft model. DHCR24 was significantly upregulated in EC and was associated with advanced FIGO stage, high tumor grade, and poor survival. Functional assays showed that DHCR24 promoted EC cell proliferation, migration, invasion, and tumor growth. Bioinformatics analyses indicated that DHCR24-associated genes were enriched in cholesterol metabolism, PI3K-Akt signaling, PPAR signaling, ECM-receptor interaction, cell cycle regulation, and cellular senescence-related pathways. Further experiments showed that DHCR24 knockdown increased p53, p21, and p16 expression and enhanced SA-β-gal staining, whereas DHCR24 overexpression produced the opposite effects. Reciprocal Co-IP assays suggested a potential association between DHCR24 and p53, indicating a possible link between DHCR24 and p53/p21/p16-related cellular senescence-like changes. Exploratory immunoinformatics analyses further suggested that DHCR24 expression may be associated with immune-related features in EC. Overall, these findings support the potential value of DHCR24 as a prognostic biomarker in EC, although further mechanistic and immunological validation is required before its therapeutic potential can be established.