Evidence map›Paper›PMID 41254141›Full record

ArticleOncogene2025

SQLE drives bladder cancer progression by boosting mitochondrial oxidative phosphorylation.

Yihong Dong, Xinjian Jiang, Xinxin Yang, Jinfeng Zhang, Qiang Fu, Yunfei Zhou, Xun Yang, Yin Fu, Yunjing Hou, Mujiao Li and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Mitochondrial function meets oncology: the multifaceted role of TFAM across cancer types.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Yihong Dong *NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Xinjian Jiang *State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Xinxin Yang *Precision Medical Center, Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
Jinfeng Zhang *State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Qiang Fu *Basic Medical College of Heilongjiang University of Chinese Medicine, Harbin, China.
Yunfei Zhou *NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Xun YangNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Yin FuBasic Medical College of Heilongjiang University of Chinese Medicine, Harbin, China.
Yunjing HouPrecision Medical Center, Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
Mujiao LiState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Jun YanNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Jianwen XuNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Yujuan YiState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Meijuan LiuState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Xiaorui HuoState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Jiang HanState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
Yumeng WangNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Chenxu GuoPrecision Medical Center, Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
Qingxin ZhangNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Aodi WuNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Xiaoqing LiDepartment of pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Xiaohan ZhangHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Shuyuan ChangNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Ayaka TomiiDepartment of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin, China.
Lin JiaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Yu XiaoHeilongjiang Province Key Laboratory of Research on Molecular Targeted Anti-Tumor Drugs, Heilongjiang, China. 102374@hrbmu.edu.cn.
Xiaoyang HuBasic Medical College of Heilongjiang University of Chinese Medicine, Harbin, China. psa1981@126.com.
Hongxue MengPrecision Medical Center, Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China. menghongxue@hrbmu.edu.cn.ORCID 0000-0002-1831-2737
Dabin LiuNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China. liudb526@126.com.ORCID 0000-0002-3811-8317
Shuijie LiState Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China. shuijie.li@hrbmu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273225National Natural Science Foundation of China (National Science Foundation of China) 82273244
6 · The paper itself

Abstract

Bladder cancer (BCa) remains a prevalent malignancy with limited therapeutic options. Although cholesterol elevation links to BCa progression, the specific role of cholesterol metabolism remains unclear. Here, we demonstrate that squalene epoxidase (SQLE), a key cholesterol biosynthesis enzyme, drives BCa oncogenesis. SQLE is upregulated in BCa patients and correlates with poor survival. Functionally, bladder-specific Sqle transgenic (tg) mice showed accelerated tumorigenesis, while Sqle knockout (ko) demonstrated opposite effects in vivo. Mechanistically, SQLE localizes to mitochondria and directly interacts with Lon peptidase 1 (LONP1) to stabilize mitochondrial transcription factor A (TFAM) by preventing its proteolysis, leading to elevated oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mtROS). Pharmacological clearance of mtROS via Mito-TEMPO suppressed tumor growth in Sqle-overexpressing models. Importantly, the FDA-approved SQLE inhibitor terbinafine significantly suppressed BCa progression in preclinical models. Our findings establish SQLE as a critical regulator of mitochondrial metabolism in BCa, supporting SQLE inhibitors as potential therapeutics. In bladder cancer, overexpression of SQLE impairs LONP1-mediated TFAM degradation through direct interaction with LONP1, thereby leading to increased mitochondrial OXPHOS and the accumulation of mtROS, which ultimately contributes to tumor growth. Treatment with the SQLE inhibitor terbinafine effectively blocks this process, providing a potential therapeutic strategy to inhibit tumor progression. The Graphical Abstract was created using Smart.Servie ( https://smart.servier.com/citation-sharing/ ).

Indexed as

MitochondriaOxidative PhosphorylationSqualene MonooxygenaseUrinary Bladder NeoplasmsAnimalsCell Line, TumorDisease ProgressionDNA-Binding ProteinsFemaleHumansMiceMice, TransgenicMitochondrial ProteinsReactive Oxygen SpeciesTranscription FactorsDNA-Binding ProteinsMitochondrial ProteinsReactive Oxygen SpeciesSqualene MonooxygenaseTranscription Factors

Identifiers

PMID41254141
PMCPMC12657232

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.