Department of Experimental Therapeutics, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
PLoS One. 2011;6(9):e24950. doi: 10.1371/journal.pone.0024950. Epub 2011 Sep 30.
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.
转移是前列腺癌患者死亡的最常见原因。鉴定特定的转移生物标志物和新的治疗靶点被认为是改善预后和疾病管理的关键。微小 RNA（miRNA）是一类非编码的小 RNA 分子，被认为是基因表达的关键调节因子。已经表明它们的失调在癌症的发生、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 可能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鉴定来源于一个患者原发癌的可移植转移性和非转移性前列腺癌异种移植系中的差异表达 miRNA。异种移植通过将癌组织植入 NOD/SCID 小鼠的肾包膜下进行，这种方法倾向于保留原始癌症的特性（例如肿瘤异质性、遗传特征）。
鉴定出差异表达的已知 miRNA、isomiRs 和 36 个新的 miRNA。其中一些 miRNA（21/104）在前列腺癌与正常前列腺组织相比时已经被报道具有类似的下调或上调，其中一些 miRNA（例如 miR-16、miR-34a、miR-126*、miR-145、miR-205）与前列腺癌转移有关，支持了分析方法的有效性。
使用源自一个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，使得本研究中鉴定的差异表达 miRNA 很可能包括人类前列腺癌转移的潜在生物标志物和/或治疗靶点。
