Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1
Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1
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miRNA-637 减少是一种不利的预后标志物，可通过直接靶向 Akt1 促进神经胶质瘤细胞生长、迁移和侵袭
DOI：
10.1038/onc.2014.419
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发表时间：
2015-09-17
期刊：
影响因子：
8
通讯作者：
Qi, S.
中科院分区：
文献类型：
--
作者：
Que, T.;Song, Y.;Qi, S.
尽管越来越多的证据表明 microRNA (miRNA) 的失调有助于肿瘤发生和侵袭，但人们对 miR-637 在人类神经胶质瘤中的作用知之甚少。在本研究中，我们发现与正常脑组织相比，临床胶质瘤组织中miR-637的表达水平显着降低。此外，我们发现miR-637的引入显着抑制了神经胶质瘤细胞在体外和体内的生长、迁移和侵袭。进一步的研究表明Akt1是miR-637的直接靶基因。沉默Akt1通过减少磷酸化Akt、β-catenin、磷酸化Foxo1和Cyclin D1并诱导Foxo1表达来抑制胶质瘤细胞的生长和侵袭，这与miR-637过表达的作用一致。 miR-637 表达抑制和 Akt1 蛋白水平升高分别与不利进展和不良预后相关，并且在神经胶质瘤中观察到 miR-637 表达与 Akt1 蛋白水平之间呈负相关。我们的研究结果为 miR-637 在神经胶质瘤发展中的作用提供了新的见解，并暗示了 miR-637 在癌症治疗中的潜在应用。
Although increasing evidence indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and invasion, little is known about the role of miR-637 in human gliomas. In the present study, we found that the expression level of miR-637 was significantly reduced in clinical glioma tissues compared with normal brain tissues. Moreover, we revealed that the introduction of miR-637 dramatically suppressed glioma cell growth, migration and invasion in vitro and in vivo. Further studies revealed that Akt1 is a direct target gene of miR-637. Silencing of Akt1 inhibited the growth and invasion of glioma cells by decreasing phosphorylated Akt, β-catenin, phosphorylated Foxo1 and Cyclin D1 and inducing the expression of Foxo1, which was consistent with the effect of miR-637 overexpression. Suppressed expression of miR-637 and increased Akt1 protein levels were correlated with unfavorable progression and poor prognosis, respectively, and a negative relationship between the miR-637 expression and Akt1 protein levels was observed in gliomas. Our findings provide new insights into the role of miR-637 in the development of gliomas, and implicate the potential application of miR-637 in cancer therapy.