Subramanian S, Lui W O, Lee C H, Espinosa I, Nielsen T O, Heinrich M C, Corless C L, Fire A Z, van de Rijn M
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Oncogene. 2008 Mar 27;27(14):2015-26. doi: 10.1038/sj.onc.1210836. Epub 2007 Oct 8.
MicroRNAs (miRNAs) are approximately 22 nucleotide-long noncoding RNAs involved in several biological processes including development, differentiation and proliferation. Recent studies suggest that knowledge of miRNA expression patterns in cancer may have substantial value for diagnostic and prognostic determinations as well as for eventual therapeutic intervention. We performed comprehensive analysis of miRNA expression profiles of 27 sarcomas, 5 normal smooth muscle and 2 normal skeletal muscle tissues using microarray technology and/or small RNA cloning approaches. The miRNA expression profiles are distinct among the tumor types as demonstrated by an unsupervised hierarchical clustering, and unique miRNA expression signatures were identified in each tumor class. Remarkably, the miRNA expression patterns suggested that two of the sarcomas had been misdiagnosed and this was confirmed by reevaluation of the tumors using histopathologic and molecular analyses. Using the cloning approach, we also identified 31 novel miRNAs or other small RNA effectors in the sarcomas and normal skeletal muscle tissues examined. Our data show that different histological types of sarcoma have distinct miRNA expression patterns, reflecting the apparent lineage and differentiation status of the tumors. The identification of unique miRNA signatures in each tumor type may indicate their role in tumorigenesis and may aid in diagnosis of soft tissue sarcomas.
微小RNA(miRNA)是长度约为22个核苷酸的非编码RNA,参与包括发育、分化和增殖在内的多种生物学过程。最近的研究表明,了解癌症中miRNA的表达模式可能对诊断和预后判定以及最终的治疗干预具有重要价值。我们使用微阵列技术和/或小RNA克隆方法,对27例肉瘤、5例正常平滑肌组织和2例正常骨骼肌组织的miRNA表达谱进行了全面分析。如无监督层次聚类所示,不同肿瘤类型的miRNA表达谱各不相同,并且在每个肿瘤类别中都鉴定出了独特的miRNA表达特征。值得注意的是,miRNA表达模式表明其中两例肉瘤被误诊,通过对肿瘤进行组织病理学和分子分析重新评估,这一点得到了证实。使用克隆方法,我们还在检测的肉瘤和正常骨骼肌组织中鉴定出31种新型miRNA或其他小RNA效应分子。我们的数据表明,不同组织学类型的肉瘤具有不同的miRNA表达模式,反映了肿瘤明显的谱系和分化状态。在每种肿瘤类型中鉴定出独特的miRNA特征可能表明它们在肿瘤发生中的作用,并可能有助于软组织肉瘤的诊断。