Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece.
J Urol. 2012 Aug;188(2):615-23. doi: 10.1016/j.juro.2012.03.122. Epub 2012 Jun 15.
miRNAs are noncoding RNAs that posttranscriptionally regulate gene expression. Altered expression and function have been observed in bladder cancer. We analyzed the expression profile of a group of miRNAs involved in bladder cancer angiogenesis, tumor cell proliferation, tumor suppressor inhibition, epithelial-mesenchymal transition and metastasis activation. Prognostic and diagnostic value, and validated targets were further examined.
Using quantitative real-time polymerase chain reaction 77 bladder cancer cases and 77 matched tumor associated normal samples were investigated to determine the expression of miR-10b, 19a, 19b, 21, 126, 145, 205, 210, 221, 296-5p and 378. The relationship between miRNA expression, patient survival and tumor pathological features was also examined.
miR-10b, 19a, 126, 145, 221, 296-5p and 378 were significantly down-regulated in bladder cancer compared to adjacent normal urothelium. miR-145 was the most down-regulated microRNA of this group. miR-19b, 21, 205 and 210 showed no significant difference between the 2 tissue types. High miR-21 expression correlated with worse overall patient survival (p = 0.0099). Multivariate analysis revealed that miR-21, 210 and 378 may serve as independent prognostic factors for overall patient survival (p = 0.005, 0.033 and 0.012, respectively). miR-21 and 378 may serve as independent prognostic factors for recurrence (p = 0.030 and 0.031, respectively). miR-145, 221, 296-5p and 378 showed the best combined ROC curves for specificity and sensitivity. miRWalk analysis was used to identify validated miRNA target genes. Further Gene Ontology enrichment revealed the main classes of biological functions of these validated targets.
Most miRNAs analyzed are down-regulated in bladder cancer. They may serve as candidate biomarkers for diagnostic and prognostic purposes in the future.
miRNAs 是非编码 RNA，可在后转录水平调节基因表达。在膀胱癌中观察到表达和功能的改变。我们分析了一组参与膀胱癌血管生成、肿瘤细胞增殖、肿瘤抑制抑制、上皮-间充质转化和转移激活的 miRNA 的表达谱。进一步检查了预后和诊断价值以及验证的靶标。
使用定量实时聚合酶链反应，对 77 例膀胱癌病例和 77 例匹配的肿瘤相关正常样本进行检测，以确定 miR-10b、19a、19b、21、126、145、205、210、221、296-5p 和 378 的表达情况。还检查了 miRNA 表达、患者生存与肿瘤病理特征之间的关系。
与相邻正常尿路上皮相比，miR-10b、19a、126、145、221、296-5p 和 378 在膀胱癌中明显下调。miR-145 是该组下调最明显的 microRNA。miR-19b、21、205 和 210 在 2 种组织类型之间无显著差异。高 miR-21 表达与患者总生存较差相关（p = 0.0099）。多变量分析显示，miR-21、210 和 378 可能是总患者生存的独立预后因素（p = 0.005、0.033 和 0.012）。miR-21 和 378 可能是复发的独立预后因素（p = 0.030 和 0.031）。miR-145、221、296-5p 和 378 显示出最佳的特异性和敏感性联合 ROC 曲线。miRWalk 分析用于鉴定验证的 miRNA 靶基因。进一步的基因本体富集分析揭示了这些验证靶标的主要生物学功能类别。
大多数分析的 miRNA 在膀胱癌中下调。它们可能成为未来诊断和预后目的的候选生物标志物。
