Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
Genes Chromosomes Cancer. 2011 Oct;50(10):812-22. doi: 10.1002/gcc.20902. Epub 2011 Jul 11.
Lung cancer is one of the deadliest types of cancer proven by the poor survival and high relapse rates after surgery. Recently discovered microRNAs (miRNAs), small noncoding RNA molecules, play a crucial role in modulating gene expression networks and are directly involved in the progression of a number of human cancers. In this study, we analyzed the expression profile of 858 miRNAs in 38 Estonian nonsmall cell lung cancer (NSCLC) samples (Stage I and II) and 27 adjacent nontumorous tissue samples using Illumina miRNA arrays. We found that 39 miRNAs were up-regulated and 33 down-regulated significantly in tumors compared with normal lung tissue. We observed aberrant expression of several well-characterized tumorigenesis-related miRNAs, as well as a number of miRNAs whose function is currently unknown. We show that low expression of miR-374a in early-stage NSCLC is associated with poor patient survival. The combinatorial effect of the up- and down-regulated miRNAs is predicted to most significantly affect pathways associated with cell migration, differentiation and growth, and several signaling pathways that contribute to tumorigenesis. In conclusion, our results demonstrate that expression of miR-374a at early stages of NSCLC progression can serve as a prognostic marker for patient risk stratification and may be a promising therapeutic target for the treatment of lung cancer.
肺癌是一种致命的癌症类型，其手术治疗后的生存率低和复发率高已得到证实。最近发现的 microRNAs（miRNAs）是一类小的非编码 RNA 分子，在调节基因表达网络方面发挥着关键作用，并且直接参与了多种人类癌症的进展。在这项研究中，我们使用 Illumina miRNA 阵列分析了 38 份爱沙尼亚非小细胞肺癌（NSCLC）样本（I 期和 II 期）和 27 份相邻非肿瘤组织样本中 858 个 miRNAs 的表达谱。与正常肺组织相比，我们发现肿瘤中有 39 个 miRNAs 上调，33 个 miRNAs 下调显著。我们观察到一些特征明确的与肿瘤发生相关的 miRNAs 表达异常，以及一些目前功能未知的 miRNAs。我们表明，miR-374a 在早期 NSCLC 中的低表达与患者生存不良相关。上调和下调 miRNAs 的组合效应预计会最显著地影响与细胞迁移、分化和生长以及几个促进肿瘤发生的信号通路相关的途径。总之，我们的研究结果表明，miR-374a 在 NSCLC 进展早期的表达可以作为患者风险分层的预后标志物，并且可能是治疗肺癌的有前途的治疗靶点。
