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Bladder cancer is one of the most common and deadly cancer worldwide. Current chemotherapy has shown limited efficacy in improving outcomes for patients. Nitroxoline, an old and widely used oral antibiotic, which was known to treat for urinary tract infection for decades. Recent studies suggested that nitroxoline suppressed the tumor progression and metastasis, especially in bladder cancer. However, the underlying mechanism for anti-tumor activity of nitroxoline remains unclear. CircRNA microarray was used to explore the nitroxoline-mediated circRNA expression profile of bladder cancer lines. Transwell and wound-healing assay were applied to evaluate the capacity of metastasis. ChIP assay was chosen to prove the binding of promotor and transcription factor. RNA-pulldown assay was performed to explore the sponge of circRNA and microRNA. We first identified the circNDRG1 (has_circ_0085656) as a novel candidate circRNA. Transwell and wound-healing assay demonstrated that circNDRG1 inhibited the metastasis of bladder cancer. ChIP assay showed that circNDRG1 was regulated by the transcription factor EGR1 by binding the promotor of host gene NDRG1. RNA-pulldown assay proved that circNDRG1 sponged miR-520h leading to the overexpression of smad7, which was a negative regulatory protein of EMT. Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

膀胱癌是全球最常见和最致命的癌症之一。目前的化疗在改善患者预后方面显示出有限的疗效。硝呋太尔是一种古老且广泛使用的口服抗生素，几十年来一直用于治疗尿路感染。最近的研究表明，硝呋太尔抑制肿瘤的进展和转移，特别是在膀胱癌中。然而，硝呋太尔的抗肿瘤活性的潜在机制尚不清楚。

我们首先鉴定出 circNDRG1（has_circ_0085656）作为一种新型候选 circRNA。Transwell 和划痕愈合实验表明 circNDRG1 抑制膀胱癌的转移。ChIP 实验表明，circNDRG1 受转录因子 EGR1 调控，通过结合宿主基因 NDRG1 的启动子。RNA 下拉实验证明 circNDRG1 可以吸附 miR-520h，导致 EMT 的负调控蛋白 smad7 过表达。

我们的研究表明，硝呋太尔可能通过 EGR1/circNDRG1/miR-520h/smad7/EMT 信号通路抑制膀胱癌的转移。