Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
J Orthop Res. 2010 Jun;28(6):746-52. doi: 10.1002/jor.21055.
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 miRNA 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.
新兴证据表明，癌症中的 microRNA（miRNA）表达特征可能具有重要的诊断、预后和治疗价值，但 chordoma 中 miRNA 表达的数据尚不清楚。本研究的目的是确定 miRNA 在人类 chordoma 中的作用。我们使用 miRNA 微阵列技术对 chordoma 衍生细胞系和 chordoma 组织进行 miRNA 表达分析，并进行无监督层次聚类分析。通过实时定量 RT-PCR 和 Northern blot 分析确认这些 miRNA 的相对表达水平。为了表征 miRNA-1 的潜在作用，我们将 miRNA-1 稳定转染到 chordoma 细胞系 UCH1 中。还研究了 miRNA-1 在 chordoma 组织中靶向基因 Met 的表达。我们观察到，通过比较 miRNA 表达谱，可以区分人类 chordoma 组织和细胞系与正常肌肉组织。与对照组相比，在 chordoma 细胞系中存在几个差异表达的 miRNA，并且在原发性 chordoma 组织中也发现了相似的表达模式。重要的是，我们首次能够证明，据我们所知，miRNA-1 和 miRNA-206 的表达在 chordoma 组织和细胞系中均显著降低，这两种 miRNA 在许多其他癌症类型中均涉及。当将 miRNA-1 转染到 chordoma 细胞系中时，观察到已知的 miRNA-1 靶基因的下调。这些靶基因包括 Met 和 HDAC4——在 chordoma 中观察到过表达的两个基因。我们的结果表明，一些 miRNA 在 chordoma 中差异表达，特别是 miRNA-1 可能对 chordoma 肿瘤发病机制具有功能影响。
