Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
Cancer Res. 2011 Jan 1;71(1):78-86. doi: 10.1158/0008-5472.CAN-10-1869.
To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer.
为了全面描述乳腺癌中的 microRNA（miRNA）表达，我们对这种疾病进行了首次广泛的下一代测序表达分析。我们对肿瘤和肿瘤相邻乳腺组织的配对样本中的小 RNA 进行了测序。我们的结果表明，肿瘤的身份主要是通过一组常见的 miRNA 表达水平的变化而不是组织特异性表达来实现的。我们还报告了 361 个新的、有充分依据的 miRNA 前体。这些新基因中有近三分之二在其他人体组织中被检测到，49%的 miRNA 与 MCF7 细胞中的 Ago2 相关。新 miRNA 的 10%位于乳腺癌中基因组高水平扩增的区域。一个新的 miRNA 编码在 ERBB2/Her2 基因内，并且该基因的扩增导致新 miRNA 的过表达，表明这个强大的致癌基因和重要的临床标志物可能具有两种不同的生物学功能。总之，我们的工作大大扩展了已知 miRNA 的数量，并突出了乳腺癌中小 RNA 表达的复杂性。
