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

This study aimed to clarify the mechanisms of E2F transcription factor 1 (E2F1) in the Cholesterol (CHOL) synthesis of Prostate cancer (PCa). 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. 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. E2F1 enhanced cell proliferation, invasion, and tumor growth by enhancing CHOL synthesis via the SND1/ACLY axis in PCa models. This study explored how a protein called E2F transcription factor 1 (E2F1) affects prostate cancer growth by regulating cholesterol production. High levels of E2F1 and two other related proteins, staphylococcal nuclease domain-containing protein 1 (SND1) and ATP citrate lyase (ACLY), were found in human prostate cancer tissues. E2F1 increased the prostate cancer cell growth and cholesterol production in the lab. The mechanism involved E2F1 increasing SND1 activity, which led to more ACLY and more cholesterol. Tests in a mouse model confirmed that E2F1 promoted cholesterol synthesis and tumor growth in prostate cancer. The E2F1/SND1/ACLY pathway in cholesterol production may offer new targets for developing clinical treatments for prostate cancer.