Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, 3234 MERF, Iowa City, IA 52242, USA.
Oncol Rep. 2011 Oct;26(4):995-1002. doi: 10.3892/or.2011.1372. Epub 2011 Jul 1.
microRNAs (miRNAs) control a multitude of pathways in human cancers. Differential expression of miRNAs among different histological types of tumors within the same type of tissue offers insight into the mechanism of pathogenesis and may help to direct treatment to improve prognosis. We assessed expression of 667 miRNAs in endometrial endometrioid and serous adenocarcinomas using RNA extracted from benign endometrium as well as from primary endometrial tumors. Quantitative miRNA profiling of endometrial adenocarcinomas revealed four overlapping groups of significantly overexpressed and underexpressed miRNAs. The first group was composed of 20 miRNAs significantly dysregulated in both adenocarcinoma types compared with benign endometrium, two groups were composed of miRNAs significantly dysregulated in either endometrioid adenocarcinomas or in serous adenocarcinomas compared with benign endometrium, and the fourth group was composed of 17 miRNAs that significantly distinguished between endometrioid adenocarcinomas and serous adenocarcinomas themselves. Validation of the expression levels of the selected miRNAs was carried out in a second panel composed of ten endometrioid and five serous tumors. Experimentally validated mRNA targets of these dysregulated miRNAs were identified using published sources, whereas TargetScan was used to predict targets of miRNAs in the first and fourth profile groups. These validated and potential miRNA target lists were filtered using published lists of genes displaying significant overexpression or underexpression in endometrial cancers compared to benign endometrium. Our results revealed a number of dysregulated miRNAs that are commonly found in endometrial (and other) cancers as well as several dysregulated miRNAs not previously identified in endometrial cancers. Understanding these differences may permit the development of both prognostic and diagnostic biomarkers.
microRNAs (miRNAs) 调控着人类癌症中的多种途径。在同一组织类型的不同组织学类型的肿瘤中，miRNAs 的差异表达提供了发病机制的深入了解，并可能有助于指导治疗以改善预后。我们使用从良性子宫内膜和原发性子宫内膜肿瘤中提取的 RNA，评估了 667 种 miRNA 在子宫内膜子宫内膜样腺癌和浆液性腺癌中的表达。子宫内膜腺癌的定量 miRNA 分析揭示了四个重叠的显著过度表达和表达不足的 miRNA 组。第一组由 20 个在两种腺癌类型中与良性子宫内膜相比明显失调的 miRNA 组成，两组由在子宫内膜样腺癌或浆液性腺癌中与良性子宫内膜相比明显失调的 miRNA 组成，第四组由 17 个在子宫内膜样腺癌和浆液性腺癌本身之间明显区分的 miRNA 组成。在由 10 个子宫内膜样癌和 5 个浆液性腺癌组成的第二个小组中进行了选定 miRNA 表达水平的验证。使用已发表的资源鉴定这些失调 miRNA 的实验验证的 mRNA 靶标，而 TargetScan 则用于预测前两个和第四个分析组中 miRNA 的靶标。使用与良性子宫内膜相比在子宫内膜癌中显示出显著过表达或表达不足的基因的已发表列表，对这些验证和潜在的 miRNA 靶标列表进行了过滤。我们的结果揭示了一些在子宫内膜癌（和其他）中常见的失调 miRNA，以及一些以前在子宫内膜癌中未发现的失调 miRNA。了解这些差异可能允许开发预后和诊断生物标志物。
