Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway

硝基喹啉通过 EGR1/circNDRG1/miR-520h/smad7/EMT 信号通路抑制膀胱癌转移

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作者:Liangliang Ren, Minxiao Jiang, Dingwei Xue, Huan Wang, Zeyi Lu, Lifeng Ding, Haiyun Xie, Ruyue Wang, Wenqin Luo, Li Xu, Mingchao Wang, Shicheng Yu, Sheng Cheng, Liqun Xia, Haifeng Yu, Peng Huang, Naijin Xu, Gonghui Li

Conclusions

Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

Methods

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.

Results

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. Conclusions: Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

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