Department of Biomarker Discovery, Exiqon A/S, Bygstubben 9, DK-2950 Vedbk, Denmark.
Mol Cancer Ther. 2011 Mar;10(3):375-84. doi: 10.1158/1535-7163.MCT-10-0605. Epub 2011 Jan 20.
MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. They are involved in many biological processes, including development, differentiation, apoptosis, and carcinogenesis. Because miRNAs may play a role in the initiation and progression of cancer, they comprise a novel class of promising diagnostic and prognostic molecular markers and potential drug targets. By applying an LNA-enhanced microarray platform, we studied the expression profiles of 955 miRNAs in the NCI-60 cancer cell lines and identified tissue- and cell-type-specific miRNA patterns by unsupervised hierarchical clustering and statistical analysis. A comparison of our data to three previously published miRNA expression studies on the NCI-60 panel showed a remarkably high correlation between the different technical platforms. In addition, the current work contributes expression data for 369 miRNAs that have not previously been profiled. Finally, by matching drug sensitivity data for the NCI-60 cells to their miRNA expression profiles, we found numerous drug-miRNAs pairs, for which the miRNA expression and drug sensitivity profiles were highly correlated and thus represent potential candidates for further investigation of drug resistance and sensitivity mechanisms.
微小 RNA（miRNA）是一组短的非编码 RNA，在转录后水平调节基因表达。它们参与许多生物学过程，包括发育、分化、凋亡和致癌作用。由于 miRNA 可能在癌症的发生和进展中发挥作用，因此它们构成了一类有前途的新型诊断和预后分子标志物和潜在的药物靶点。我们应用 LNA 增强的微阵列平台，研究了 NCI-60 癌细胞系中 955 个 miRNA 的表达谱，并通过无监督层次聚类和统计分析确定了组织和细胞类型特异性 miRNA 模式。将我们的数据与 NCI-60 小组的三个先前发表的 miRNA 表达研究进行比较，显示不同技术平台之间具有非常高的相关性。此外，目前的工作为以前未进行过分析的 369 个 miRNA 提供了表达数据。最后，通过将 NCI-60 细胞的药物敏感性数据与 miRNA 表达谱进行匹配，我们发现了许多药物 miRNA 对，其 miRNA 表达和药物敏感性谱高度相关，因此代表了进一步研究耐药性和敏感性机制的潜在候选物。
