Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease
Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease
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DOI：
10.1002/ijc.26405
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发表时间：
2012-08-01
影响因子：
6.4
通讯作者：
Butler, Lisa M.
中科院分区：
文献类型：
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作者：
Selth, Luke A.;Townley, Scott;Butler, Lisa M.
循环microRNAs （miRNAs）正在成为有用的非侵入性疾病标志物。本研究的目的是使用前列腺癌小鼠模型作为发现可在临床环境中评估的血清mirna的工具。全球miRNA分析发现，与健康对照组相比，晚期前列腺癌转基因腺癌小鼠（TRAMP）血清中的46种miRNA水平显著改变（p = 0.05）。在一个独立的小鼠队列中验证了这些具有已知人类同源物的mirna的一个子集，然后在转移性去势抵抗性前列腺癌（mCRPC, n = 25）或健康男性（n = 25）的血清中进行了测量。在小鼠中改变的四种mirna， mmu-miR-141, mmu-miR-298， mmu-miR-346和mmu-miR-375，也被发现在mCRPC男性的血清中处于不同水平。与正常前列腺组织相比，其中三种（hsa-miR-141、hsa-miR-298和hsa-miR-375）在前列腺肿瘤中表达上调，表明它们随着疾病的进展被释放到血液中。此外，肿瘤内hsa-miR-141和hsa-miR-375的表达是手术后生化复发的预测因子。这项研究首次证明了特异性血清mirna在人类前列腺癌和该疾病的小鼠模型之间是共同的，突出了这种模型在发现新的生物标志物方面的潜力。
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.