Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Int J Cancer. 2012 Aug 1;131(3):652-61. doi: 10.1002/ijc.26405. Epub 2011 Nov 3.


Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p ≤ 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration-resistant prostate cancer (mCRPC; n = 25) or healthy men (n = 25). Four miRNAs altered in mice, mmu-miR-141, mmu-miR-298, mmu-miR-346 and mmu-miR-375, were also found to be at differential levels in the serum of men with mCRPC. Three of these (hsa-miR-141, hsa-miR-298 and hsa-miR-375) were upregulated in prostate tumors compared with normal prostate tissue, suggesting that they are released into the blood as disease progresses. Moreover, the intra-tumoral expression of hsa-miR-141 and hsa-miR-375 were predictors of biochemical relapse after surgery. This study is the first to demonstrate that specific serum miRNAs are common between human prostate cancer and a mouse model of the disease, highlighting the potential of such models for the discovery of novel biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Gene Expression Profiling
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology


  • Biomarkers, Tumor
  • MIRN141 microRNA, human
  • MIRN298 microRNA, human
  • MIRN375 microRNA, human
  • MicroRNAs