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Research Paper|Volume 12, Issue 8|pp 6865—6879

Circular RNA circRGNEF promotes bladder cancer progression via miR-548/KIF2C axis regulation

Chen Yang1,2,3, Qiong Li4, Xinan Chen1,2, Zheyu Zhang1,2, Zezhong Mou1,2, Fangdie Ye1,2, Shengming Jin5, Xiang Jun6, Feng Tang4, Haowen Jiang1,2,3
  • 1Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China
  • 2Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China
  • 3National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai 200032, China
  • 4Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China
  • 5Shanghai Cancer Center, Fudan University, Shanghai 200040, China
  • 6Department of Urinary Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
* Equal contribution
Received: February 8, 2020Accepted: March 9, 2020Published: April 19, 2020
https://doi.org/10.18632/aging.103047

Copyright © 2020 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Circular RNAs (circRNAs) play an important role in bladder cancer (BC). Though circRNA involvement in BC has been reported, the underlying regulatory mechanisms are unknown. In this study, we performed EdU, CCK8, colony formation and Transwell assays to establish the role of circRGNEF in BC cell migration, proliferation, and invasion. We used bioinformatics and luciferase reporter experiments to investigate the regulatory mechanism. Nude mice xenografts and live imaging were used to explore the role of circRGNEF in tumor metastasis and growth. Expression profile analysis of human circRNAs in BC revealed that circRGNEF was upregulated significantly. High circRGNEF expression was correlated with aggressive BC phenotypes. The downregulation of circRGNEF suppressed BC cell metastasis and proliferation by targeting the miR-548/KIF2C axis in vitro and in vivo; these results were verified with luciferase reporter assays. Our results show that miR-548 downregulation or KIF2C overexpression restored BC cell proliferation, migration, and invasion following silencing of circRGNEF. KIF2C overexpression reversed miR-548-induced cell invasion and migration as well as growth inhibition in vitro. In summary, the data illustrate that circRGNEF suppresses BC progression by functioning as a miR-548 sponge to enhance KIF2C expression. Therefore, circRGNEF might be a candidate BC treatment target.