Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/72884
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Type: Journal article
Title: Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease
Author: Selth, L.
Townley, S.
Gillis, J.
Ochnik, A.
Murti, K.
Macfarlane, R.
Chi, K.
Marshall, V.
Tilley, W.
Butler, L.
Citation: International Journal of Cancer, 2012; 131(3):652-661
Publisher: Wiley-liss
Issue Date: 2012
ISSN: 0020-7136
1097-0215
Statement of
Responsibility: 
Luke A. Selth, Scott Townley, Joanna L. Gillis, Aleksandra M. Ochnik, Krisna Murti, Robyn J. Macfarlane, Kim N. Chi, Villis R. Marshall, Wayne D. Tilley and Lisa M. Butler
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 5 25) or healthy men (n 5 25). Four miRNAs altered in mice, mmumiR- 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.
Keywords: Animals
Mice, Inbred C57BL
Mice, Transgenic
Humans
Mice
Prostatic Neoplasms
MicroRNAs
Prognosis
Oligonucleotide Array Sequence Analysis
Gene Expression Profiling
Male
Biomarkers, Tumor
Rights: Copyright © 2011 UICC
DOI: 10.1002/ijc.26405
Grant ID: http://purl.org/au-research/grants/nhmrc/627185
Appears in Collections:Aurora harvest 5
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