MicroRNA-133b suppresses bladder cancer malignancy by targeting TAGLN2-mediated cell cycle

J Cell Physiol. 2019 Apr;234(4):4910-4923. doi: 10.1002/jcp.27288. Epub 2018 Oct 14.

Abstract

MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3'-untranslated regions (3'-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.

Keywords: TAGLN2; bladder cancer; cell cycle; miR-133b; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Microfilament Proteins / metabolism*
  • Muscle Proteins / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / genetics*
  • Transplantation, Heterologous
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / prevention & control*

Substances

  • MIRN133 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Muscle Proteins
  • Tagln2 protein, human