DHCR24 overexpression is involved in lipid metabolic reprogramming to drive cervical cancer malignant progression and is associated with immune microenvironment

DHCR24 过表达参与脂质代谢重编程,从而驱动宫颈癌的恶性进展,并且与免疫微环境相关。

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Abstract

OBJECTIVE: Lipid metabolic reprogramming enables tumor cells to acquire malignant phenotypes, including enhanced proliferative capacity, migratory potential, and invasive properties. In cervical cancer, the precise pathobiological roles and molecular mechanisms of DHCR24 remain unclear. METHODS: We performed comprehensive bioinformatics analyses to investigate the expression patterns, clinical relevance, and prognostic implications of DHCR24 in cervical carcinoma. A prognostic nomogram incorporating tumor stage and DHCR24 expression levels was developed to predict clinical outcomes in patients. Functional studies using SiHa cell lines were conducted to elucidate the oncogenic properties of DHCR24. We used a cholesterol kit to determine the cholesterol content in cervical cancer cells. Finally, we assessed the association between DHCR24 expression and tumor immune microenvironment characteristics through computational analysis of public genomic datasets. RESULTS: Our analysis revealed significantly elevated DHCR24 expression in cervical carcinoma specimens, demonstrating statistically significant associations with histological subtype, body mass index (BMI), and therapeutic response (P < 0.05). Univariate and Multivariate Cox regression confirmed DHCR24 as an independent prognostic indicator for cervical cancer. The ROC analysis demonstrates that DHCR24 exhibits robust diagnostic performance for cervical cancer detection. Pharmacological inhibition of DHCR24 using U18666A markedly attenuated oncogenic behaviors, suppressing cellular proliferation, migration, and invasion compared to controls (P < 0.05). Notably, intracellular cholesterol levels exhibited a dose-dependent reduction corresponding to the extent of DHCR24 suppression. CONCLUSIONS: We hypothesized that DHCR24 is involved in reprogramming lipid metabolism, especially the cholesterol pathway, to promote tumor progression in cervical cancer and correlates with the tumor-infiltrating immune microenvironment. DHCR24 is a biomarker that predicts the progression and prognosis of cervical cancer and is one of the potential targets for cervical cancer therapy.

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