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|Title:||Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease|
|Citation:||International Journal of Cancer, 2012; 131(3):652-661|
|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|
|Appears in Collections:||Medicine publications|
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