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

Aging (Albany NY). 2020 Apr 19;12(8):6865-6879. doi: 10.18632/aging.103047. Epub 2020 Apr 19.


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.

Keywords: KIF2C; bladder cancer; circRGNEF; circular RNA; miR-548.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • HEK293 Cells
  • Humans
  • Kinesins / genetics*
  • Kinesins / metabolism
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA, Small Interfering
  • Up-Regulation
  • Urinary Bladder / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*


  • ARHGEF28 protein, human
  • Guanine Nucleotide Exchange Factors
  • KIF2C protein, human
  • MIRN548 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • Kinesins