Gaur Arti, Jewell David A, Liang Yu, Ridzon Dana, Moore Jason H, Chen Caifu, Ambros Victor R, Israel Mark A
Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03755, USA.
Cancer Res. 2007 Mar 15;67(6):2456-68. doi: 10.1158/0008-5472.CAN-06-2698.
MicroRNAs are small noncoding RNAs that function by regulating target gene expression posttranscriptionally. They play a critical role in developmental and physiologic processes and are implicated in the pathogenesis of several human diseases including cancer. We examined the expression profiles of 241 human microRNAs in normal tissues and the NCI-60 panel of human tumor-derived cell lines. To quantify microRNA expression, we employed a highly sensitive technique that uses stem-loop primers for reverse transcription followed by real-time PCR. Most microRNAs were expressed at lower levels in tumor-derived cell lines compared with the corresponding normal tissue. Agglomerative hierarchical clustering analysis of microRNA expression revealed four groups among the NCI-60 cell lines consisting of hematologic, colon, central nervous system, and melanoma tumor-derived cell lines clustered in a manner that reflected their tissue of origin. We identified specific subsets of microRNAs that provide candidate molecular signatures characteristic of the tumor-derived cell lines belonging to these four clusters. We also identified specific microRNA expression patterns that correlated with the proliferation indices of the NCI-60 cell lines, and we developed evidence for the identification of specific microRNAs as candidate oncogenes and tumor suppressor genes in different tumor types. Our results provide evidence that microRNA expression patterns may mark specific biological characteristics of tumors and/or mediate biological activities important for the pathobiology of malignant tumors. These findings call attention to the potential of microRNAs to provide etiologic insights as well as to serve as both diagnostic markers and therapeutic targets for many different tumor types.
微小RNA是一类小的非编码RNA，通过转录后调控靶基因表达发挥作用。它们在发育和生理过程中起关键作用，并与包括癌症在内的多种人类疾病的发病机制有关。我们检测了241种人类微小RNA在正常组织和NCI-60人肿瘤衍生细胞系中的表达谱。为了定量微小RNA的表达，我们采用了一种高度灵敏的技术，该技术使用茎环引物进行逆转录，随后进行实时PCR。与相应的正常组织相比，大多数微小RNA在肿瘤衍生细胞系中的表达水平较低。对微小RNA表达进行的凝聚层次聚类分析显示，NCI-60细胞系可分为四组，包括血液学、结肠、中枢神经系统和黑色素瘤肿瘤衍生细胞系，其聚类方式反映了它们的组织来源。我们鉴定出了微小RNA的特定子集，这些子集提供了属于这四个簇的肿瘤衍生细胞系的候选分子特征。我们还鉴定出了与NCI-60细胞系增殖指数相关的特定微小RNA表达模式，并为在不同肿瘤类型中鉴定特定微小RNA作为候选癌基因和肿瘤抑制基因提供了证据。我们的结果表明，微小RNA表达模式可能标志着肿瘤的特定生物学特征和/或介导对恶性肿瘤病理生物学重要的生物学活性。这些发现提请人们注意微小RNA在提供病因学见解以及作为许多不同肿瘤类型的诊断标志物和治疗靶点方面的潜力。
