Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer

Br J Cancer. 2012 Jan 17;106(2):405-13. doi: 10.1038/bjc.2011.462. Epub 2011 Nov 8.


Background: Our recent analyses of miRNA expression signatures showed that miR-1 and miR-133a were significantly reduced in several types of cancer. Interestingly, miR-1 and miR-133a are located on the same chromosomal locus in the human genome. We examined the functional significance of miR-1 and miR-133a in prostate cancer (PCa) cells and identified the novel molecular targets regulated by both miR-1 and miR-133a.

Methods and results: The expression levels of miR-1 and miR-133a were significantly downregulated in PCa compared with non-PCa tissues. Restoration of miR-1 or miR-133a in PC3 and DU145 cells revealed significant inhibition of proliferation, migration, and invasion. Molecular target identification by genome-wide gene expression analysis and luciferase reporter assay showed that purine nucleoside phosphorylase (PNP) was directly regulated by both miRNAs. Silencing of the PNP gene inhibited proliferation, migration, and invasion in both PC3 and DU145 cells. Immunohistochemistry detected positive staining of PNP in PCa specimens.

Conclusions: Downregulation of miR-1 and miR-133a was a frequent event in PCa and both function as tumour suppressors. The PNP is a novel target gene of both miRNAs and potentially functions as an oncogene. Therefore, identification of novel molecular networks regulated by miRNAs may provide new insights into the underlying causes of PCa oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation
  • Genes, Tumor Suppressor*
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Purine-Nucleoside Phosphorylase / genetics
  • Purine-Nucleoside Phosphorylase / metabolism*
  • RNA Processing, Post-Transcriptional
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • MIRN1 microRNA, human
  • MIRN133 microRNA, human
  • MicroRNAs
  • Purine-Nucleoside Phosphorylase