The James Buchanan Brady Urologic Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
The Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sci Rep. 2018 May 8;8(1):7189. doi: 10.1038/s41598-018-25320-z.
MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.
miR-1 和 miR-143 在人类前列腺癌 (PCa) 中经常减少，而 miR-141 和 miR-21 经常增加。因此，这些 miRNA 已被研究为细胞自主的肿瘤抑制因子和癌基因。然而，这些 miRNA 在前列腺组织中的细胞类型特异性尚未得到很好的定义。通过两种不同的显微切割技术和液滴数字 RT-PCR，我们在根治性前列腺切除术标本的基质和上皮中定量了这些 miRNA。与它们作为细胞自主肿瘤抑制因子的假定作用相反，我们发现 miR-1 和 miR-143 的表达主要是基质的。相反，miR-141 主要是上皮的。miR-21 在上皮和基质中均有检测到。引人注目的是，肿瘤相关基质中的 miR-1 和 miR-143 水平显著降低，但肿瘤上皮中没有。人类细胞系、组织和前列腺衍生的基质培养物中的基因表达分析支持 miR-1、miR-141 和 miR-143 的细胞类型选择性表达。对 PCa 基因组图谱 (TCGA-PRAD) 的分析表明，基质标记物与 miR-1 和 miR-143 之间存在强烈的正相关，而基质标记物与 miR-141 之间存在强烈的负相关。在这些肿瘤中，miR-1 的丢失和 miR-21 的获得与生化复发高度相关。这些数据为 PCa 肿瘤微环境中的基质和上皮 miRNA 表达提供了新的见解。
