Differential Expression of microRNA (miRNA) in Chordoma Reveals a Role for miRNA-1 in Met Expression
Differential Expression of microRNA (miRNA) in Chordoma Reveals a Role for miRNA-1 in Met Expression
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DOI：
10.1002/jor.21055
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发表时间：
2010-06-01
影响因子：
2.8
通讯作者：
Hornicek, Francis J.
中科院分区：
文献类型：
--
作者：
Duan, Zhenfeng;Choy, Edwin;Hornicek, Francis J.
新出现的证据表明，微小RNA（miRNA）在癌症中的表达特征可能具有重要的诊断，预后和治疗价值，但没有关于脉络膜中miRNA表达的数据。本研究的目的是鉴定miRNAs在人类脉络膜中的作用。我们通过使用miRNA微阵列技术和无监督的层次聚类分析来分析脊索瘤源性细胞系和脊索组织中的mRNA表达。通过实时定量RT-PCR和北方印迹分析证实这些miRNA的相对表达水平。为了表征miRNA-1的潜在作用，将miRNA-1稳定转染到脉络膜细胞系UCH 1中。同时检测了miRNA-1靶基因Met在脉络膜组织中的表达。我们观察到人类脉络膜组织和细胞系可以通过比较miRNA表达谱与正常肌肉组织区分开来。与对照组相比，几种miRNA在脉络膜细胞系中差异表达，并且在原代脉络膜组织中发现了相似的表达模式。重要的是，据我们所知，我们首次能够证明，在脉络膜组织和细胞系中，miRNA-1和miRNA-206（与许多其他癌症类型有关的两种miRNA）的表达显著降低。当用miRNA-1转染脉络膜细胞系时，观察到已知的miRNA-1靶标下调。这些靶标包括Met和HDAC 4-观察到在脉络膜中过表达的两个基因。我们的研究结果表明，一些miRNA在脉络膜中差异表达，特别是miRNA-1可能对脉络膜肿瘤的发病机制具有功能性影响。(C)2009骨科研究学会。由威利期刊公司出版J Orthop Res 28：746-752，2010
Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed rniRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:746-752, 2010