Wang Xinsheng, Qu Yanqing, Sun Yanbo, Yang Tong, Wang Wei, Dou Xinmeng, Jia Yong
Department of Urology, Tianjin First Central Hospital, Tianjin, 300211, China.
Surgical Clinic, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong, 266071, China.
BMC Cancer. 2025 Apr 28;25(1):789. doi: 10.1186/s12885-025-14183-z.
ATPase H transporting V0 subunit b (ATP6V0B) is an essential component of the vacuolar ATP multi-protein complex (V-ATPase) associated with energy metabolism. However, information on its role and mechanism of action in bladder cancer (BCa) and other tumors is not clear.
In this study, we evaluated the expression of ATP6V0B in BCa and its correlation with patient survival outcomes by performing public database analysis, as well as, RT-qPCR and Western blotting assays. We also investigated the effect of altering the level of expression of ATP6V0B on the malignant behavior of BCa cells at the cellular level by conducting the CCK-8 assay and Transwell assay. In vivo experiments involved subcutaneous injection of stable ATP6V0B-knockdown BCa cells into nude mice to assess the influence of ATP6V0B on tumorigenesis. Additionally, bioinformatics analysis was combined with other methods to predict that ATP6V0B may modulate signaling pathways.
The findings showed that the expression of ATP6V0B increased in BCa tissues, and patients exhibiting high levels of this protein had a poorer prognosis. Additionally, our results showed that ATP6V0B functions as an oncogene and stimulates the proliferation, invasion, and migration of BCa cells in vitro. In vivo animal studies showed that downregulating ATP6V0B hindered the growth of BCa. Regarding the mechanism of action of ATVP60VB, we found that ATVP60VB can activate the PI3K/AKT signaling pathway through Progestin and AdipoQ Receptor Family Member 4 (PAQR4) -mediated upregulation.
To summarize, the results of this study indicated that an increase in the level of expression of ATP6V0B in BCa tissues and cells is associated with unfavorable patient prognosis due to its tumor-promoting effects via upregulation of the PAQR4/PI3K/AKT signaling pathway.
ATP酶H运输V0亚基b（ATP6V0B）是与能量代谢相关的液泡ATP多蛋白复合物（V-ATP酶）的重要组成部分。然而，其在膀胱癌（BCa）和其他肿瘤中的作用及作用机制尚不清楚。
在本研究中，我们通过进行公共数据库分析以及RT-qPCR和蛋白质免疫印迹分析，评估了ATP6V0B在BCa中的表达及其与患者生存结果的相关性。我们还通过CCK-8试验和Transwell试验，在细胞水平上研究了改变ATP6V0B表达水平对BCa细胞恶性行为的影响。体内实验包括将稳定敲低ATP6V0B的BCa细胞皮下注射到裸鼠体内，以评估ATP6V0B对肿瘤发生的影响。此外，生物信息学分析与其他方法相结合，预测ATP6V0B可能调节信号通路。
研究结果表明，ATP6V0B在BCa组织中的表达增加，且该蛋白水平高的患者预后较差。此外，我们的结果表明，ATP6V0B作为一种癌基因，在体外刺激BCa细胞的增殖、侵袭和迁移。体内动物研究表明，下调ATP6V0B可抑制BCa的生长。关于ATVP60VB的作用机制，我们发现ATVP60VB可通过孕激素和脂联素受体家族成员4（PAQR4）介导的上调激活PI3K/AKT信号通路。
总之，本研究结果表明，BCa组织和细胞中ATP6V0B表达水平的升高与患者预后不良有关，因为它通过上调PAQR4/PI3K/AKT信号通路具有促肿瘤作用。
