microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2

Biosci Rep. 2021 Jan 29;41(1):BSR20201000. doi: 10.1042/BSR20201000.

Abstract

Background: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer.

Methods: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo.

Results: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo.

Conclusions: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

Keywords: EN2; bladder cancer; miR-27b; therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Computational Biology / methods
  • Disease Progression
  • Female
  • Heterografts
  • Homeodomain Proteins / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Nerve Tissue Proteins / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Homeodomain Proteins
  • MIRN27b microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • engrailed 2 protein