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
School of Public Health, Guangxi Medical University, Nanning, 530021, China.
Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, 530021, China.
Cell Biol Toxicol. 2025 May 28;41(1):91. doi: 10.1007/s10565-025-10038-2.
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.
长期暴露于砷（As）这种普遍存在的环境污染物中，会显著增加多种癌症的风险，包括膀胱癌和肺癌。近年来，环状RNA（circRNA）在肿瘤发生和发展中的重要作用已引起广泛关注。然而，circRNA在砷暴露后促进膀胱癌发展的具体分子机制仍不完全清楚。本研究首次证明，circPDE3B在砷引发的细胞转化模型中显著上调，并促进这一转化过程。我们的研究阐明了circPDE3B在体外SV-HUC-1细胞中的生物学功能，表明它通过增加细胞增殖和抑制凋亡来加速砷诱导的恶性转化。此外，我们还描绘了一种新的分子机制，即circPDE3B直接与NF-κB和STAT3结合，抑制它们的泛素化并增加其稳定性。这反过来又影响下游HIF-1α的表达，促进SV-HUC-1细胞的恶性转化，最终导致膀胱癌的发生。我们的研究揭示了circPDE3B在砷诱导的SV-HUC-1细胞恶性转化中的关键调控作用。这项研究为推动膀胱癌进展的分子机制提供了更广阔的视角，同时也确定了膀胱癌早期诊断和治疗的潜在靶点。
