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p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth

Huishan Sun1, Li Li1, Wei Li1

  • 1State Key Laboratory of Medical Molecular Biology, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

EMBO Reports
|August 30, 2021
PubMed

Insights

The tumor suppressor p53 directly inhibits cholesterol synthesis by repressing the enzyme SQLE. This pathway suppresses tumor growth and liver cancer, highlighting SQLE as a therapeutic target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Cholesterol is vital for cell functions, including proliferation and differentiation.
  • Its role in cancer and synthesis regulation remains an active research area.

Purpose of the Study:

  • To investigate the role of p53 in regulating cholesterol synthesis.
  • To explore the impact of SQLE regulation on tumor growth and liver tumorigenesis.

Main Methods:

  • Investigated p53's regulation of SQLE expression under normal sterol conditions.
  • Utilized siRNA, terbinafine, and shRNA to inhibit or silence SQLE.
  • Examined the effects of SQLE modulation and cholesterol levels on cell proliferation.
  • Assessed the impact of SQLE inhibition on liver tumorigenesis in p53 knockout mice.

Main Results:

  • p53 directly represses SQLE expression independently of SREBP2.
  • Downregulation of SQLE by p53 reduces cholesterol production, suppressing tumor growth.
  • SQLE inhibition reverses proliferation increases in p53-deficient cells.
  • SQLE inhibition restricts NAFLD-induced liver tumorigenesis in p53 knockout mice.

Conclusions:

  • p53 plays a critical role in regulating cholesterol biosynthesis via SQLE.
  • Downregulation of SQLE is essential for p53-mediated tumor suppression.
  • Targeting SQLE shows potential for restricting liver tumorigenesis.
Keywords:
SQLEcell proliferationcholesterolp53

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