MicroRNA-195 suppresses tumor cell proliferation and metastasis by directly targeting BCOX1 in prostate carcinoma

J Exp Clin Cancer Res. 2015 Sep 4;34(1):91. doi: 10.1186/s13046-015-0209-7.

Abstract

Elucidation of the downstream targets regulated by the metastasis-suppressive miRNAs can shed light on the metastatic processes in prostate cancer (PCa). We conducted microarray analyses and found that miR-195 was significantly decreased in metastatic PCa. Low miR-195 expression is an independent prognostic factor for poor biochemical recurrence-free and overall survival. Forced expression of miR-195 in PCa cells drastically inhibits proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo. BCOX1 is identified as a direct target of miR-195 in PCa, and is found to be drastically increased in metastatic PCa. BCOX1 knockdown phenotypically copies miR-195-induced phenotypes, whereas forced expression of BCOX1 reverses the effects of miR-195. Collectively, this is the first report unveils that loss of miR-195 expression and thus uncontrolled BCOX1 upregulation might drive PCa metastasis.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice, Nude
  • MicroRNAs / physiology*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm Transplantation
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA Interference

Substances

  • KIAA0100 protein, human
  • MIRN195 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins