Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs.
Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs.
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DOI：
10.1186/1471-2407-14-82
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发表时间：
2014-02-11
期刊：
影响因子：
3.8
通讯作者：
Fuessel S
中科院分区：
文献类型：
--
作者：
Erdmann K;Kaulke K;Thomae C;Huebner D;Sergon M;Froehner M;Wirth MP;Fuessel S
最近的证据表明，前列腺癌（PCa）特异性上调某些基因，如AMACR，EZH 2，PSGR，PSMA和TRPM 8可能与非编码microRNA（miRNA）的异常表达有关。使用计算机模拟分析来搜索作为PCa相关基因的推定调节因子的miRNA。9种选择的miRNAs的表达（hsa-miR-101，-138，-186，-224，-26a，-26b，-374a，-410，-660）以及上述PCa相关基因通过定量PCR使用50个恶性肿瘤（Tu）和匹配的非恶性肿瘤（Tf）进行分析。来自前列腺切除术标本的组织样品以及来自良性前列腺增生（BPH）患者的30个样品。然后分析配对miRNA与靶基因表达水平之间的相关性。此外，在各种PCa细胞系中通过定量PCR和Western印迹确定外源施用的miR-26 a对所选靶基因的影响。荧光素酶报告基因测定用于靶标验证。与任一对照组相比，PCa组织样品中所有选定的miRNA的表达均降低（Tu vs Tf：-1.35至-5.61倍; Tu vs BPH：-1.17至-5.49倍）。大多数miRNAs的下调与其推定靶基因的上调呈负相关，斯皮尔曼相关系数范围为-0.107至-0.551。miR-186在非器官局限性PCa和初始转移的患者中显示出显著降低的表达。此外，miR-26 a的过表达还可降低其潜在靶基因AMACR的mRNA和蛋白表达。使用荧光素酶报告基因测定，验证AMACR为miR-26 a的新靶点。这项研究的结果表明，特定的miRNA的表达在PCa中减少，并与其推定的靶基因的上调呈负相关。因此，miRNA可能通过改变miRNA-靶基因相互作用而促进PCa的肿瘤发生和进展。
Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction.
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影响因子：
64.8
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通讯作者：
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