Inhibition of miR-1247 on cell proliferation and invasion in bladder cancer through its downstream target of RAB36

J Biosci. 2018 Jun;43(2):365-373.

Abstract

Recently, microRNA-1247 (miR-1247) has been reported to function as tumour suppressor in several cancer types, including pancreatic cancer, hepatocellular cancer and lung cancer. However, the biological function of miR-1247 in bladder cancer and the underlying mechanisms have remained largely uncovered. In this study, the expression of miR-1247 was significantly downregulated, while RAB36 protein was remarkably upregulated in bladder cancer tissues and cell lines compared with that in paired adjacent normal tissues or normal cell line (SU-HUC-1). The function of miR-1247 and RAB36 in the cell viability, proliferation and invasion of bladder cancer cells (T24 and J82) was assessed by CCK-8, colony formation and Transwell assay, respectively. Gain of function studies showed that upregulation of miR-1247 significantly inhibited cell proliferation and invasion capacity of bladder cancer cells. Consistently, downregulation of RAB36 mimicked the suppressive effects of miR-1247 overexpression in bladder cancer cells. Importantly, miR-1247 was confirmed to target the 30untranslated region (UTR) of RAB36 and downregulated its expression using luciferase reporter assay and Western blot assays. In conclusion, these results provide the first clues regarding the role of miR-1247 might be a potential therapeutic agent and diagnostic marker of bladder cancer by inhibiting RAB36 expression.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • rab GTP-Binding Proteins / genetics*

Substances

  • MIRN1247 microRNA, human
  • MicroRNAs
  • Rab36 protein, human
  • rab GTP-Binding Proteins