Knockouts of CYP51A1, DHCR24, or SC5D from cholesterol synthesis reveal pathways modulated by sterol intermediates.

ABSTRACT: Sterols from cholesterol synthesis are crucial for cholesterol production, but also have individual roles difficult to assess in vivo due to essentiality of cholesterol. We developed HepG2 cell models with knockouts (KOs) for three enzymes of cholesterol synthesis, each accumulating specific sterols. Surprisingly, KOs of CYP51, DHCR24, and SC5D shared only 9% of differentially expressed genes. The most striking was the phenotype of CYP51 KO with highly elevated lanosterol and 24,25-dihydrolanosterol, significant increase in G2+M phase and enhanced cancer and cell cycle pathways. Comparisons with mouse liver Cyp51 KO data suggest 24,25-dihydrolanosterol activates similar cell proliferation pathways, possibly via elevated LEF1 and WNT/NFKB signaling.

SUBMITTER: Skubic C 

PROVIDER: S-EPMC11387598 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature