Abstract
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.
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Acknowledgements
This study was supported by the National Nature Science Fund of China (NO.81372692; http://www.nsfc.gov.cn), the Natural Science Fund of Guangdong Province (NO.S2013010014886; http://www.gdstc.gov.cn), the Medical Scientific Research Fund of Guangdong Province (NO.B2013238; http://www.medste.gd.cn), the Scientific Research Initiative Project Fund of Southern Medical University (NO.B1012032; http://www.fimmu.com), the President Fund of Nanfang Hospital (2011C007, 2012C011; http://www.nfyy.com), the Science Fund of the Affiliated Hospital of Luzhou Medical College (2013-60) and Science and Technology Project of Luzhou (3-S-48). The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript.
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Que, T., Song, Y., Liu, Z. et al. Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1. Oncogene 34, 4952–4963 (2015). https://doi.org/10.1038/onc.2014.419
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DOI: https://doi.org/10.1038/onc.2014.419
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