Wang Tingjun, Wang Gang, Shan Danni, Fang Yayun, Zhou Fenfang, Yu Mengxue, Ju Lingao, Li Gang, Xiang Wan, Qian Kaiyu, Zhang Yi, Xiao Yu, Wang Xinghuan
Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cancer. 2024 Apr 23;15(11):3297-3312. doi: 10.7150/jca.95549. eCollection 2024.
Acetyl-CoA acetyltransferase 1 (ACAT1) plays a significant role in the regulation of gene expression and tumorigenesis. However, the biological role of ACAT1 in bladder cancer (BLCA) has yet to be elucidated. This research aimed to elucidate the bioinformatics features and biological functions of ACAT1 in BLCA. Here, we demonstrate that is elevated in BLCA tissues and is correlated with specific clinicopathological features and an unfavorable prognosis for survival in BLCA patients. was identified as an independent risk factor in BLCA. Phenotypically, both and , knockdown suppressed BLCA cell proliferation and migration, while ACAT1 overexpression had the opposite effect. Mechanistic assays revealed that ACAT1 enhances BLCA cell proliferation and metastasis through the AKT/GSK3β/c-Myc signaling pathway by modulating the cell cycle and EMT. Taken together, the results of our study reveal that ACAT1 is an oncogenic driver in BLCA that enhances tumor proliferation and metastasis, indicating its potential as a diagnostic and therapeutic target for this disease.
乙酰辅酶A乙酰基转移酶1(ACAT1)在基因表达调控和肿瘤发生中起重要作用。然而,ACAT1在膀胱癌(BLCA)中的生物学作用尚未阐明。本研究旨在阐明ACAT1在BLCA中的生物信息学特征和生物学功能。在此,我们证明ACAT1在BLCA组织中升高,且与特定的临床病理特征以及BLCA患者的不良生存预后相关。ACAT1被确定为BLCA的独立危险因素。在表型上,ACAT1敲低和敲除均抑制BLCA细胞增殖和迁移,而ACAT1过表达则产生相反的效果。机制分析表明,ACAT1通过调节细胞周期和上皮-间质转化,通过AKT/GSK3β/c-Myc信号通路增强BLCA细胞增殖和转移。综上所述,我们的研究结果表明,ACAT1是BLCA中的致癌驱动因子,可增强肿瘤增殖和转移,表明其作为该疾病诊断和治疗靶点的潜力。