CircZFR serves as a prognostic marker to promote bladder cancer progression by regulating miR-377/ZEB2 signaling

Biosci Rep. 2019 Dec 20;39(12):BSR20192779. doi: 10.1042/BSR20192779.

Abstract

Circular RNAs (circRNAs) have been identified as crucial regulators of gene expression in human cancer biology. CircZFR is a novel identified circRNA and its effect in bladder cancer remains unclearly. In the present study, we aimed to investigate the role of circZFR in the progression of bladder cancer. First, we demonstrated that the expression of circZFR was higher in bladder cancer tissues and cells compared with adjacent non-tumor tissues and normal bladder epithelial cells. And higher circZFR levels were positively correlated with bladder cancer patients' pathological T stage, grade, lymphatic metastasis, recurrence, progression-free survival (PFS) and overall survival (OS). Functionally, knockdown of circZFR could significantly prohibit cell growth, migration and invasion, arrest cell cycle as well as promote apoptosis of bladder cancer cells in vitro study. Mechanistically, we observed that circZFR could directly bind to miR-377 as sponge to promote ZEB2 expression in bladder cancer cells. In addition, rescue assays demonstrated that restoration of ZEB2 significantly impaired the suppressive effects of circZFR silencing on bladder cancer cells growth, migration and invasion. Taken together, our results illuminated that circZFR could be a prognostic biomarker in bladder cancer and exerted oncogenic roles through regulating miR-377/ZEB2 axis in bladder cancer, which indicated that circZFR could be a potential therapeutic target for bladder cancer patients treatment.

Keywords: Bladder cancer; CircZFR; Prognostic biomarker; ZEB2; miR-377.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Zinc Finger E-box Binding Homeobox 2 / genetics
  • Zinc Finger E-box Binding Homeobox 2 / metabolism*

Substances

  • Biomarkers, Tumor
  • MIRN377 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Circular
  • RNA, Neoplasm
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2