Zou Fan, Chen Wu, Song Tianbao, Xing Ji, Zhang Yunlong, Chen Kang, Hu Weimin, Li Linzhi, Ning Jinzhuo, Li Chenglong, Yu Weimin, Cheng Fan
Department of Urology, Renmin Hospital of Wuhan University, 99 ziyang road, Wuhan, 430060, Hubei Province, China.
Department of Urology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cancer Cell Int. 2023 Sep 28;23(1):221. doi: 10.1186/s12935-023-02997-5.
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.
膀胱癌（BCa）是全球最常见的恶性肿瘤之一。然而，缺乏准确有效的靶向药物已成为当前BCa临床治疗中的一个主要问题。研究表明，角鲨烯环氧酶（SQLE）作为胆固醇生物合成中的关键限速酶，参与癌症发展。在本研究中，我们对癌症基因组图谱（The Cancer Genome Atlas）、基因型-组织表达（The Genotype-Tissue Expression）和基因表达综合数据库（Gene Expression Omnibus）的分析显示，SQLE在癌组织中的表达显著高于相邻正常组织，且SQLE高表达的BCa组织预后较差。然后，我们在qRT-PCR和免疫组织化学染色实验中证实了这一结果，并且我们的体外研究表明，敲低SQLE可通过PTEN/AKT/GSK3β信号通路抑制肿瘤细胞增殖和转移。通过拯救实验，我们证明P53是SQLE介导的PTEN/AKT/GSK3β信号通路调控中的关键分子。同时，我们通过裸鼠成瘤实验验证了上述发现。总之，我们的研究表明，SQLE通过P53/PTEN/AKT/GSK3β轴促进BCa生长，这可能成为BCa的一个治疗生物学靶点。
