Institute of Medical Technology, University of Tampere, Tampere University Hospital, Finland.
Genes Chromosomes Cancer. 2011 Jul;50(7):499-509. doi: 10.1002/gcc.20873. Epub 2011 Mar 31.
MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate the expression of protein coding genes. In this study, we screened highly informative prostate cancer cell lines and xenografts (n = 42) for miRNA gene copy number and expression changes. The expression profiling showed distinction between cell lines and xenografts as well as between androgen sensitive and independent models. Only a few copy number alterations that were associated with expression changes were identified. Most importantly, the miR-15a-miR-16-1 locus was found to be homozygously deleted in two samples leading to the abolishment of miR-15a, but not miR-16, expression. miR-16 is also expressed from another genomic locus. Mutation screening of the miR-15a-miR-16-1 gene in the model systems as well as clinical samples (n = 50) revealed no additional mutations. In conclusion, our data indicate that putative tumor suppressors, miR-15a and miR-16-1, are homozygously deleted in a subset of prostate cancers, further suggesting that these miRNAs could be important in the development of prostate cancer.
MicroRNAs (miRNAs) 是小的非编码 RNA,可以负调控蛋白质编码基因的表达。在本研究中,我们筛选了高信息量的前列腺癌细胞系和异种移植(n = 42),以检测 miRNA 基因拷贝数和表达变化。表达谱分析显示细胞系和异种移植之间以及雄激素敏感和独立模型之间存在差异。仅鉴定出少数与表达变化相关的拷贝数改变。最重要的是,发现两个样本中的 miR-15a-miR-16-1 基因座发生纯合缺失,导致 miR-15a 但不 miR-16 的表达被废除。miR-16 也从另一个基因组座表达。在模型系统和临床样本(n = 50)中对 miR-15a-miR-16-1 基因进行突变筛选未发现其他突变。总之,我们的数据表明,某些前列腺癌中存在潜在的肿瘤抑制因子 miR-15a 和 miR-16-1 的纯合缺失,进一步表明这些 miRNA 在前列腺癌的发生中可能很重要。