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Inhibition of SQLE or FDFT1 in RBE cells by shRNA, or RBE cells treated with lycorine hydrochloride

ABSTRACT: High-throughput sequencing was performed to analyze gene expression profiles of RBE cells after the the inhibition of SQLE or FDFT1 by lentiviruses-mediated shRNA, or RBE cells treated with lycorine hydrochloride.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240746 | GEO | 2023/08/18

REPOSITORIES: GEO

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Inhibition of SQLE or FDFT1 in RBE cells by shRNA, or RBE cells treated with lycorine hydrochloride

Project description:Inhibition of SQLE or FDFT1 in RBE cells by shRNA, or RBE cells treated with lycorine hydrochloride

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p53 transcriptionally regulates SQLE to modulate cholesterol synthesis and tumor growth

Project description:Cholesterol is essential for membrane biogenesis, cell proliferation and differentiation. The role of cholesterol in cancer development and the regulation of cholesterol synthesis are still under active investigation. Here we show that under normal-sterol conditions，p53 directly represses the expression of SQLE, a rate-limiting and the first oxygenation enzyme in cholesterol synthesis，in a SREBP2-independent manner. Through transcriptional downregulation of SQLE, p53 represses cholesterol production in vivo and in vitro, leading to tumor growth suppression. Inhibition of SQLE using small interfering RNA (siRNA) or terbinafine (a SQLE inhibitor) reverses the increased cell proliferation caused by p53 deficiency. Conversely, SQLE overexpression or cholesterol addition promotes cell proliferation, particularly in p53 wild-type cells. More importantly, pharmacological inhibition or shRNA-mediated silencing of SQLE restricts nonalcoholic fatty liver disease (NAFLD) -induced liver tumorigenesis in p53 knockout mice. Therefore, our findings reveal a role for p53 in regulating SQLE and cholesterol biosynthesis, and further demonstrate that downregulation of SQLE is critical for p53-mediated tumor suppression.

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Effect of depletion of SQLE on gene expression of B16F10 Melanoma cells in vivo

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RNA sequencing to determine gene expression changes in SQLE knockdown osteosarcoma cells

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Expression data from human Bladder cancer cell line J82 with control or overexpression of SQLE

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Liver transcriptome study in lambs

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