Characterization of microRNA expression levels and their biological correlates in human cancer cell lines
Characterization of microRNA expression levels and their biological correlates in human cancer cell lines
复制标题
DOI：
10.1158/0008-5472.can-06-2698
复制
发表时间：
2007-03-15
期刊：
影响因子：
11.2
通讯作者：
Israel, Mark A.
中科院分区：
文献类型：
--
作者：
Gaur, Arti;Jewell, David A.;Israel, Mark A.
MicroRNA是一类非编码小分子RNA，通过转录后调节靶基因的表达发挥作用。它们在发育和生理过程中发挥关键作用，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microRNA在正常组织和NCI-60人类肿瘤细胞系中的表达谱。为了定量microRNA的表达，我们采用了一种高灵敏度的技术，该技术使用茎环引物进行逆转录，然后进行实时PCR。与相应的正常组织相比，大多数microRNA在肿瘤来源的细胞系中的表达水平较低。microRNA表达的聚集层次聚类分析显示，在由血液、结肠、中枢神经系统和黑色素瘤肿瘤来源的细胞系组成的NCI-60细胞系中，有四组以反映其来源组织的方式聚类。我们鉴定了microRNA的特定子集，其提供了属于这四个簇的肿瘤衍生细胞系的候选分子特征。我们还鉴定了与NCI-60细胞系增殖指数相关的特定microRNA表达模式，并为鉴定特定microRNA作为不同肿瘤类型中的候选癌基因和肿瘤抑制基因提供了证据。我们的研究结果提供的证据表明，microRNA的表达模式可能标志着特定的肿瘤生物学特性和/或介导的生物学活性的恶性肿瘤的病理生物学重要。这些发现引起了人们对microRNA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的潜力的关注。
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.