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环状KDM4C通过miR-200bc-3p/ZEB1轴增强膀胱癌的侵袭和转移。

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

作者信息

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

机构信息

Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Cancer Center, Zhejiang University, Hangzhou, 310058, China.

出版信息

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

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.

摘要

环状RNA(circRNAs)在人类膀胱癌(BCa)发展过程中发挥着重要作用,然而,circRNAs在BCa中的异常表达模式和功能失调尚未得到评估。在本研究中,我们验证了源自KDM4C基因的circKDM4C(hsa_circ_0001839)在BCa细胞系和组织中均有上调。在功能上,circKDM4C的过表达显著增强,而circKDM4C的沉默则抑制了BCa细胞的迁移和侵袭能力。机制上,circKDM4C可作为一种miRNA海绵直接与miR-200b-3p和miR-200c-3p相互作用,从而增强ZEB1的表达并促进间充质表型。总之,我们的研究结果表明,circKDM4C可能通过circKDM4C/miR-200bc-3p/ZEB1轴在BCa侵袭和转移中作为一种促癌因子发挥作用,这是膀胱癌的一个潜在生物标志物或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ec/8608878/ebad6efdd652/41420_2021_712_Fig1_HTML.jpg

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