title: Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease.
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.
authors: Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, University of Adelaide, Hanson Institute, Adelaide, South Australia, Australia. luke.selth@adelaide.edu.au
authors: Luke A
authors: LA
authors: Selth
authors: Scott
authors: S
authors: Townley
authors: Joanna L
authors: JL
authors: Gillis
authors: Aleksandra M
authors: AM
authors: Ochnik
authors: Krisna
authors: K
authors: Murti
authors: Robyn J
authors: RJ
authors: Macfarlane
authors: Kim N
authors: KN
authors: Chi
authors: Villis R
authors: VR
authors: Marshall
authors: Wayne D
authors: WD
authors: Tilley
authors: Lisa M
authors: LM
authors: Butler
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C533895:MIRN141 microRNA, human; C569760:MIRN298 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs