miR-205 Exerts Tumor-Suppressive Functions in Human Prostate through Down-regulation of Protein Kinase Cε
miR-205 Exerts Tumor-Suppressive Functions in Human Prostate through Down-regulation of Protein Kinase Cε
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DOI：
10.1158/0008-5472.can-08-2894
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发表时间：
2009-03-15
期刊：
影响因子：
11.2
通讯作者：
Zaffaroni, Nadia
中科院分区：
文献类型：
--
作者：
Gandellini, Paolo;Folini, Marco;Zaffaroni, Nadia
关于微小rna在前列腺癌中的表达和作用的信息有限。在这项研究中，我们研究了miR-205在前列腺癌发生中的作用。与正常前列腺细胞系相比，miR-205在癌症中的表达水平显著降低，与匹配的正常前列腺组织相比，肿瘤中的miR-205表达水平显著降低，尤其是在局部区域弥散性疾病患者的癌中。恢复前列腺癌细胞中miR-205的表达导致了与间质向上皮转变相一致的细胞重排，例如E-cadherin的上调和细胞运动和侵袭的减少，以及一些已知参与疾病进展的癌基因（即白细胞介素）的下调。6，洞穴蛋白-1，EZH2)。我们的证据表明，这些事件是由miR-205特异性预测靶点（即N-chimaerin、ErbB3、E2F1、E2F5、ZEB2和蛋白激酶C epsilon）的同时抑制所驱动的。引人注目的是，后者似乎在调节上皮细胞到间质细胞的转变中起直接作用。事实上，它的下调导致细胞表型在很大程度上与异位表达miR-205的细胞相似。总体而言，我们首次发现miR-205通过抑制上皮细胞到间质细胞的转化和减少细胞迁移/侵袭，在人类前列腺中发挥肿瘤抑制作用，至少部分是通过下调蛋白激酶C epsilon。[癌症研究2009；69 (6): 2287 - 95)
Limited information is available concerning the expression and role of microRNAs in prostate cancer. In this study, we investigated the involvement of miR-205 in prostate carcinogenesis. Significantly lower miR-205 expression levels were found in cancer than in normal prostate cell lines as well as in tumor compared with matched normal prostate tissues, with a particularly pronounced reduction in carcinomas from patients with local-regionally disseminated disease. Restoring the expression of miR-205 in prostate cancer cells resulted in cell rearrangements consistent with a mesenchymal-to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell locomotion and invasion, and in the down-regulation of several oncogenes known to be involved in disease progression (i.e., interleukin. 6, caveolin-1, EZH2). Our evidence suggests that these events are driven by the concurrent repression of specific predicted miR-205 targets, namely N-chimaerin, ErbB3, E2F1, E2F5, ZEB2, and protein kinase C epsilon. Strikingly, the latter seemed to play a direct role in regulating epithelial-to-mesenchymal transition. In fact, its down-regulation led to a cell phenotype largely reminiscent of that of cells ectopically expressing miR-205. Overall, we showed for the first time that miR-205 exerts a tumor-suppressive effect in human prostate by counteracting epithelial-to-mesenchymal transition and reducing cell migration/invasion, at at least in part through the down-regulation of protein kinase C epsilon. [Cancer Res 2009;69(6):2287-95]