E2F1-driven cholesterol synthesis via the SND1/ACLY axis potentiates malignant progression in prostate cancer

Aim: This study aimed to clarify the mechanisms of E2F transcription factor 1 (E2F1) in the Cholesterol (CHOL) synthesis of Prostate Cancer (PCa).

Methods: CHOL component content was detected using a commercial test kit. The interaction between E2F1 and staphylococcal nuclease domain-containing protein 1 (SND1) promoter was confirmed employing dual luciferase and chromatin immunoprecipitation assay. RNA immunoprecipitation and RNA pull-down analysis were utilized to validate the interaction between SND1 and ATP Citrate Lyase (ACLY) mRNA. A xenograft tumor model was used to confirm these mechanisms in vivo.

Results: E2F1, SND1, ACLY protein levels, along with CHOL concentrations, were up-regulated in human PCa tumor tissues. E2F1 enhanced cell proliferation, invasion, and CHOL synthesis in PCa cells. E2F1 could transcriptionally activate SND1, which subsequently bound to ACLY mRNA, stabilizing its expression. E2F1 induced CHOL synthesis via the enhancement of SND1/ACLY axis. E2F1 promoted CHOL synthesis and PCa tumor growth in vivo.

Conclusion: E2F1 enhanced cell proliferation, invasion, and tumor growth by enhancing CHOL synthesis via the SND1/ACLY axis in PCa models.

ACLY; CHOL synthesis; E2F1; Pca; SND1.