miR186 suppresses prostate cancer progression by targeting Twist1.
miR186 suppresses prostate cancer progression by targeting Twist1.
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miR186 通过靶向 Twist1 抑制前列腺癌进展。
DOI：
10.18632/oncotarget.8887
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Zhao X;Wang Y;Deng R;Zhang H;Dou J;Yuan H;Hou G;Du Y;Chen Q;Yu J
前列腺癌(Pca)是北美男性癌症相关死亡的第二大原因，大多数与其相关的死亡是由于晚期和转移性pca。然而，PCa进展的分子机制仍不清楚。在这里，我们使用一对具有相同遗传背景的前列腺癌细胞系P69/M12，而高转移细胞系M12是P69的一个亚系，以确定前列腺癌的发病机制。我们发现，与P69相比，M12中关键的miRNA-miR186显著减少。此外，我们证实miR186在人前列腺癌标本中也下调，在转移患者标本中最显著。MiR186的低表达与患者的生存不良有关。通过在PCa细胞系中敲除或过表达miR186，我们发现miR186通过下调其靶标Twist1而强烈抑制细胞的运动、侵袭性、软琼脂集落形成、3D培养生长和血管生成拟态(VM)形成能力，以及上皮向间充质转化(EMT)的过程。此外，在体内肿瘤转移实验和临床标本中证实了miR186和Twist1的表达水平之间的负相关关系。综上所述，我们的研究结果表明miR186/Twist1轴在调节PCa进展中起着重要作用，提示miR186/Twist1在PCa治疗中有潜在的应用价值。
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in north American men, and most its related deaths are due to advanced and metastatic PCa. However, the molecular mechanisms underlying PCa progression are still unclear. Here we use a pair of prostate cell lines P69/M12, which have the same genetic background and the highly metastatic cell line M12 is a subline derived from P69, to identify the pathogenesis of PCa. We find that a key miRNA--miR186 is significantly reduced in M12 compared to that in P69. Further, we validate that miR186 is also downregulated in human PCa specimens, most significantly in the metastatic patient specimens. The low miR186 expression is correlated with poor patient survival. Through knockdown or overexpression of miR186 in PCa cell lines, we discover that miR186 strongly inhibits cell motility, invasive, soft-agar colony formation, 3D culture growth and vasculogenic mimicry (VM) formation capacity, as well as the epithelial-to-mesenchymal transition (EMT) process by downregulation of its target Twist1. Moreover, the inverse relationship between the expression levels of miR186 and Twist1 is confirmed in vivo tumor metastasis experiment and clinical specimens. Taken together, our findings demonstrate an important role of miR186/Twist1 axis in the regulation of PCa progression, suggesting a potential application of miR186/Twist1 in PCa treatment.
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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