circKDM4C enhances bladder cancer invasion and metastasis through miR-200bc-3p/ZEB1 axis

Xueyou Ma; Yufan Ying; Jiazhu Sun; Haiyun Xie; Jiangfeng Li; Liujia He; Weiyu Wang; Shiming Chen; Haixiang Shen; Jiahe Yi; Jindan Luo; Xiao Wang; Xiangyi Zheng; Ben Liu; Liping Xie

doi:10.1038/s41420-021-00712-9

circKDM4C enhances bladder cancer invasion and metastasis through miR-200bc-3p/ZEB1 axis

Cell Death Discov. 2021 Nov 23;7(1):365. doi: 10.1038/s41420-021-00712-9.

Authors

Xueyou Ma^{1

2}, Yufan Ying^{1

2}, Jiazhu Sun^{1

2}, Haiyun Xie^{1

2}, Jiangfeng Li^{1

2}, Liujia He^{1

2}, Weiyu Wang^{1

2}, Shiming Chen^{1

2}, Haixiang Shen^{1

2}, Jiahe Yi^{1

2}, Jindan Luo^{1

2}, Xiao Wang^{1

2}, Xiangyi Zheng^{1

2}, Ben Liu^{3

4}, Liping Xie^{5

6}

Affiliations

¹ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
² Cancer Center, Zhejiang University, Hangzhou, 310058, China.
³ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. drliuben@zju.edu.cn.
⁴ Cancer Center, Zhejiang University, Hangzhou, 310058, China. drliuben@zju.edu.cn.
⁵ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. xielp@zju.edu.cn.
⁶ Cancer Center, Zhejiang University, Hangzhou, 310058, China. xielp@zju.edu.cn.

Abstract

Circular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.

Abstract

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