Demethylation of miR-195 suppresses prostate cancer cell proliferation, migration and invasion

FEBS Open Bio. 2020 Apr;10(4):525-534. doi: 10.1002/2211-5463.12799. Epub 2020 Mar 9.

Abstract

Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor-associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR-195 was reported to be hypermethylated at its promoter CpG island and down-regulated in hepatocellular carcinoma. However, the function of miR-195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down-regulation of microRNA-195 (miR-195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR-195 significantly suppressed cell proliferation, migration, invasion and epithelial-mesenchymal transition (increased E-cadherin and decreased N-cadherin) in PCa cells. We further demonstrated that transfection with a miR-195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5-azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR-195 may function as a crucial tumor suppressor in PCa.

Keywords: methylation; miR-195; prostate cancer; tumor suppressor.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Azacitidine / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • CpG Islands
  • DNA Methylation / drug effects
  • Demethylation / drug effects*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • PC-3 Cells
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Transfection

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • Azacitidine