1. Academic Validation
  2. SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53

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

  • Cancer Cell Int. 2023 Sep 28;23(1):221. doi: 10.1186/s12935-023-02997-5.
Fan Zou # 1 Wu Chen # 1 Tianbao Song # 1 Ji Xing 1 Yunlong Zhang 1 Kang Chen 2 Weimin Hu 1 Linzhi Li 1 Jinzhuo Ning 1 Chenglong Li 1 Weimin Yu 3 Fan Cheng 4
Affiliations

Affiliations

  • 1 Department of Urology, Renmin Hospital of Wuhan University, 99 ziyang road, Wuhan, 430060, Hubei Province, China.
  • 2 Department of Urology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Department of Urology, Renmin Hospital of Wuhan University, 99 ziyang road, Wuhan, 430060, Hubei Province, China. ywm.com.cn@163.com.
  • 4 Department of Urology, Renmin Hospital of Wuhan University, 99 ziyang road, Wuhan, 430060, Hubei Province, China. urology1969@aliyun.com.
  • # Contributed equally.
Abstract

Bladder Cancer (BCa) is one of the most common malignancies worldwide. However, the lack of accurate and effective targeted drugs has become a major problem in current clinical treatment of BCa. Studies have demonstrated that squalene epoxidase (SQLE), as a key rate-limiting Enzyme in Cholesterol biosynthesis, is involved in Cancer development. In this study, our analysis of The Cancer Genome Atlas, The Genotype-Tissue Expression, and Gene Expression Omnibus databases showed that SQLE expression was significantly higher in Cancer tissues than it was in adjacent normal tissues, and BCa tissues with a high SQLE expression displayed a poor prognosis. We then confirmed this result in qRT-PCR and immunohistochemical staining experiments, and our vitro studies demonstrated that SQLE knockdown inhibited tumor cell proliferation and metastasis through the PTEN/Akt/GSK3β signaling pathway. By means of rescue experiments, we proved that that P53 is a key molecule in SQLE-mediated regulation of the PTEN/Akt/GSK3β signaling pathway. Simultaneously, we verified the above findings through a tumorigenesis experiment in nude mice. In conclusion, our study shows that SQLE promotes BCa growth through the P53/PTEN/Akt/GSK3β axis, which may serve as a therapeutic biological target for BCa.

Keywords

Apoptosis; Bladder cancer; Cell cycle; P53; PTEN/AKT/GSK3β signaling pathway; Proliferation; SQLE.

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