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

Luke A Selth, Scott Townley, Joanna L Gillis, Aleksander M Ochnik, Krisna Murti, Robyn J Macfarlane, Kim N Chi, Villis R Marshall, Wayne D Tilley, Lisa M Butler

Research output: Contribution to journalReview articlepeer-review

130 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)652-661
Number of pages10
JournalInternational Journal of Cancer
Volume131
Issue number3
DOIs
Publication statusPublished - 1 Aug 2012
Externally publishedYes

Keywords

  • biomarker
  • microRNA
  • mouse model
  • prostate cancer
  • serum

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