MicroRNAs associated with metastatic prostate cancer.

MicroRNAs associated with metastatic prostate cancer.
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DOI:
10.1371/journal.pone.0024950
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Wang Y
Wang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Watahiki A;Wang Y;Morris J;Dennis K;O'Dwyer HM;Gleave M;Gout PW;Wang Y

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转移是前列腺癌患者死亡的最常见原因。特异性转移生物标志物和新的治疗靶点的鉴定被认为对于改善疾病的预后和管理至关重要。microRNA(miRNAs)是一类非编码小RNA分子,被认为是基因表达的关键调节因子。它们的失调已被证明在癌症的发病、进展和转移中起作用,并且miRNA代表了一类有前途的新的癌症生物标志物。本研究的目的是鉴定前列腺癌中下调和上调的miRNA,这些miRNA可以为前列腺癌转移提供潜在的生物标志物和/或治疗靶点。应用下一代测序技术来鉴定可移植转移性与非转移性前列腺癌异种移植物系中差异表达的miRNA,两者均来源于一名患者的原发性癌症。通过将癌组织肾包膜下移植到NOD/SCID小鼠中来开发异种移植物,这是一种倾向于保留原始癌症的性质(例如,肿瘤异质性、遗传谱)。鉴定了差异表达的已知miRNAs、isomiRs和36种新的miRNAs。先前已经报道了许多这些miRNA(21/104)在前列腺癌中相对于正常前列腺组织显示出类似的下调或上调,并且其中一些(例如,miR-16、miR-34 a、miR-126*、miR-145、miR-205)与前列腺癌转移有关,支持分析方法的有效性。来自一名患者癌症的转移性和非转移性前列腺癌肾包膜下异种移植物的使用使得本研究中鉴定的差异表达的miRNA可能包括人前列腺癌转移的潜在生物标志物和/或治疗靶标。
Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis and management of the disease. MicroRNAs (miRNAs) form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis. Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient's primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles). Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach. The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patient's cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis.
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