SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53

Fan Zou1, Wu Chen1, Tianbao Song1

  • 1Department of Urology, Renmin Hospital of Wuhan University, 99 ziyang road, Wuhan, 430060, Hubei Province, China.

Cancer Cell International
|September 28, 2023
PubMed

Insights

Squalene epoxidase (SQLE) is upregulated in bladder cancer (BCa), correlating with poor prognosis. Inhibiting SQLE suppresses BCa growth and metastasis via the P53/PTEN/AKT/GSK3β pathway, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Bladder cancer (BCa) is a prevalent malignancy with limited targeted therapies.
  • Squalene epoxidase (SQLE), a key enzyme in cholesterol biosynthesis, is implicated in cancer progression.
  • Identifying novel therapeutic targets for BCa is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of SQLE in bladder cancer development and progression.
  • To elucidate the molecular mechanisms underlying SQLE's function in BCa.
  • To evaluate SQLE as a potential therapeutic target for BCa.

Main Methods:

  • Bioinformatic analysis of The Cancer Genome Atlas, The Genotype-Tissue Expression, and Gene Expression Omnibus databases.
  • Quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining.
  • In vitro cell culture experiments (SQLE knockdown, rescue experiments) and in vivo tumorigenesis assays in nude mice.

Main Results:

  • SQLE expression is significantly elevated in BCa tissues compared to normal tissues, associated with poor prognosis.
  • SQLE knockdown inhibits BCa cell proliferation and metastasis.
  • SQLE regulates the PTEN/AKT/GSK3β signaling pathway, with P53 identified as a key mediator.

Conclusions:

  • SQLE promotes bladder cancer growth and metastasis through the P53/PTEN/AKT/GSK3β signaling axis.
  • Targeting SQLE presents a promising therapeutic strategy for bladder cancer.
  • This study identifies a novel molecular pathway critical for BCa pathogenesis.

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