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The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer

Cancer Gene Therapy volume 27, pages 189–202 (2020)Cite this article

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Abstract

Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3′-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues. Furthermore, circINTS4 was found to control multiple pathological processes, including cell proliferation and migration, the cell cycle and apoptosis. Regarding the mechanism, circINTS4 directly bound to miR-146b to inhibit its activity of targeting the 3′-UTR of CARMA3 mRNA. In addition, circINTS4 could activate the NF-kB signalling pathway and suppress the P38 MAPK signalling pathway in a CARMA3-mediated manner in BC cells. In summary, the circINTS4/miR-146b/CARMA3 axis might serve as a promising therapeutic target for BC intervention.

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Acknowledgements

This work was supported by National Natural Science Fund [Grant No. 81672525], the Project of Liaoning Distinguished Professor (Grant No. [2012]145), Liaoning Natural Science Fund [Grant No. 201602830], Shenyang Plan Project of Science and Technology (Grant No. F17-230-9-08) and Shenyang Clinical Medicine Research Center (Grant No. [2017]76), and China Medical University’s 2017 discipline promotion programme (Grant No. 2017XK08) and China Medical University’s 2018 discipline promotion programme. Funding agency did not participate in the design of the study and collection, analysis and interpretation of data, and in writing the manuscript.

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  1. Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China

    Xiaotong Zhang, Xi Liu, Zhifei Jing, Jianbin Bi, Zeliang Li, Xiankui Liu, Jun Li, Zhenhua Li, Zhe Zhang & Chuize Kong

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  1. Xiaotong Zhang
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Correspondence to Zhenhua Li, Zhe Zhang or Chuize Kong.

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Zhang, X., Liu, X., Jing, Z. et al. The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer. Cancer Gene Ther 27, 189–202 (2020). https://doi.org/10.1038/s41417-019-0085-y

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