Dyson Greg, Farran Batoul, Bolton Susan, Craig Douglas B, Dombkowski Alan, Beebe-Dimmer Jennifer L, Powell Isaac J, Podgorski Izabela, Heilbrun Lance K, Bock Cathryn H
Karmanos Cancer Institute and Department of Oncology, Wayne State University Detroit MI, USA.
Karmanos Cancer Institute and Department of Pediatrics, Wayne State University Detroit MI, USA.
Am J Cancer Res. 2018 Oct 1;8(10):2088-2095. eCollection 2018.
MicroRNAs (miRNAs) constitute short non-coding RNAs that can post-transcriptionally modulate the expression of many oncogenes and tumor suppressor genes engaged in key cellular processes. Deregulated serum miRNA signatures have been detected in various solid cancers including prostate cancer, suggesting that circulating miRNAs could function as non-invasive biomarkers of tumor emergence and progression. To determine whether serum miRNA expression levels are different between patients with aggressive and non-aggressive prostate cancer, we analyzed a panel of miRNAs from the blood of African American (AA) prostate cancer patients using a new recursive partitioning method that allows hypothesis testing of each split. We observed that both extrema of circulating miR-17, i.e. upregulation and downregulation, are associated with aggressive prostate cancer. A similar effect was observed in tumor samples from a separate dataset representing a different population of prostate cancer patients and in AA prostate cancer samples from the TCGA. The dual effect is consistent with the contradictory findings on the role of miR-17 in prostate cancer progression, whereby it controls important oncogenic and tumor-suppressive genes.
微小RNA(miRNA)是一类短链非编码RNA,可在转录后调节许多参与关键细胞过程的癌基因和肿瘤抑制基因的表达。在包括前列腺癌在内的各种实体癌中均检测到血清miRNA特征失调,这表明循环miRNA可能作为肿瘤发生和进展的非侵入性生物标志物。为了确定侵袭性和非侵袭性前列腺癌患者之间血清miRNA表达水平是否存在差异,我们使用一种新的递归划分方法分析了一组来自非裔美国(AA)前列腺癌患者血液中的miRNA,该方法允许对每次划分进行假设检验。我们观察到循环miR-17的两个极端情况,即上调和下调,均与侵袭性前列腺癌相关。在代表不同前列腺癌患者群体的另一个数据集中的肿瘤样本以及来自TCGA的AA前列腺癌样本中也观察到了类似的效果。这种双重作用与关于miR-17在前列腺癌进展中的作用的矛盾发现一致,即它控制着重要的致癌基因和肿瘤抑制基因。