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Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
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SQLE drives bladder cancer progression by boosting mitochondrial oxidative phosphorylation
Yihong Dong1, Xinjian Jiang2,3, Xinxin Yang4
1NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Oncogene
|November 18, 2025
Summary
Squalene epoxidase (SQLE), a cholesterol enzyme, drives bladder cancer (BCa) by increasing mitochondrial reactive oxygen species (mtROS). Inhibiting SQLE with terbinafine shows promise for BCa treatment.
Area of Science:
- Biochemistry
- Oncology
- Mitochondrial Metabolism
Background:
- Bladder cancer (BCa) has limited treatment options.
- Cholesterol metabolism's role in BCa is not fully understood.
Purpose of the Study:
- Investigate the role of squalene epoxidase (SQLE) in bladder cancer.
- Explore SQLE as a potential therapeutic target.
Main Methods:
- Analysis of SQLE expression in BCa patients.
- In vivo studies using bladder-specific Sqle transgenic and knockout mice.
- Mitochondrial protein interaction studies (SQLE, LONP1, TFAM).
- Assessment of oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mtROS).
- Preclinical treatment with Mito-TEMPO and terbinafine.
Main Results:
- SQLE is upregulated in BCa and linked to poor survival.
- SQLE overexpression accelerates tumor growth; knockout inhibits it.
- SQLE stabilizes TFAM via LONP1 interaction, increasing OXPHOS and mtROS.
- Mito-TEMPO and terbinafine suppressed tumor growth in preclinical models.
Conclusions:
- SQLE is a key driver of bladder cancer oncogenesis through mitochondrial metabolic reprogramming.
- Targeting SQLE with inhibitors like terbinafine is a potential therapeutic strategy for BCa.
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