Porkka Kati P, Pfeiffer Minja J, Waltering Kati K, Vessella Robert L, Tammela Teuvo L J, Visakorpi Tapio
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Cancer Res. 2007 Jul 1;67(13):6130-5. doi: 10.1158/0008-5472.CAN-07-0533.
MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P=0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer.
微小RNA(miRNA)是一类内源性表达的小非编码RNA,它们在翻译水平上对蛋白质编码基因的表达起负调控作用。越来越多的证据,如miRNA的异常表达,表明它们参与了癌症的发生发展。在各种肿瘤类型中都发现了miRNA,这表明不同的miRNA集合在不同的癌症中通常失调。为了鉴定前列腺癌特有的miRNA特征,采用寡核苷酸阵列杂交方法对6种前列腺癌细胞系、9个前列腺癌异种移植样本、4个良性前列腺增生(BPH)样本和9个前列腺癌样本进行了miRNA表达谱分析。检测到良性肿瘤和癌性肿瘤之间51种单个miRNA的差异表达,其中37种在癌性样本中呈下调,14种呈上调,从而鉴定出那些可能在前列腺癌发生和/或生长中起重要作用的miRNA。通过阵列比较基因组杂交确定的miRNA表达与miRNA基因座拷贝数之间存在显著趋势(P = 0.029),表明遗传畸变可能靶向miRNA。根据miRNA表达对肿瘤样本进行层次聚类,准确地将癌性肿瘤与BPH样本区分开来,并根据雄激素依赖性(激素初治与激素难治)对癌性肿瘤进一步分类,这表明miRNA作为前列腺癌一种新的诊断和预后工具具有潜力。