Long-term exposure to arsenic (As), which is a ubiquitous environmental contaminant, significantly enhances the risk of multiple cancers, including bladder and lung cancers. In recent years, the important roles of circular RNAs (circRNAs) in tumorigenesis and development have attracted widespread attention. However, the specific molecular mechanisms by which circRNAs promote bladder cancer development following exposure to arsenic remain incompletely understood. This study is the first to demonstrate that circPDE3B is significantly upregulated in a cell model of transformation triggered by arsenic and that it promotes this transformation process. Our study elucidated the biological function of circPDE3B in vitro, in SV-HUC-1 cells, showing that it accelerates the malignant transformation from arsenic via increasing cell proliferation and inhibiting apoptosis. Furthermore, we delineated a novel molecular mechanism whereby circPDE3B directly binds to NF-κB and STAT3, inhibiting their ubiquitination and increasing their stability. This, in turn, affects downstream HIF-1α expression, promoting the malignant transformation of SV-HUC-1 cells and eventually resulting in bladder carcinogenesis. Our research reveals the critical regulatory role of circPDE3B in the arsenic-triggered malignant transformation within SV-HUC-1 cells. This study offers broader perspectives on the molecular mechanisms driving bladder cancer progression, while also identifying potential targets for early diagnosis and treatment of bladder tumour.
The key regulator circPDE3B promotes arsenic-induced bladder carcinogenesis by affecting STAT3 and NF-κB stability.
阅读:2
作者:Gao Yihong, Xu Haotian, Zhao Qingyun, Cai Dunyu, Zhou Xiaodong, Chen Xingcai, Yuan Shengyi, Li Deqing, Ning Taoran, Dong Xiangyu, Li Mengyao, Li Gang, Nan Aruo
期刊: | Cell Biology and Toxicology | 影响因子: | 5.900 |
时间: | 2025 | 起止号: | 2025 May 28; 41(1):91 |
doi: | 10.1007/s10565-025-10038-2 |
特别声明
1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。
2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。
3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。
4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。