Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1

被引:114
作者
Que, T. [1 ,2 ]
Song, Y. [1 ]
Liu, Z. [2 ,3 ]
Zheng, S. [1 ]
Long, H. [1 ]
Li, Z. [1 ]
Liu, Y. [1 ]
Wang, G. [1 ]
Liu, Y. [1 ]
Zhou, J. [4 ]
Zhang, X. [1 ]
Fang, W. [2 ,5 ]
Qi, S. [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Neurosurg, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Canc Res Inst, Guangzhou 510515, Guangdong, Peoples R China
[3] Guangzhou Med Univ, Basic Sch, Dept Pathol, Guangzhou, Guangdong, Peoples R China
[4] Luzhou Med Coll, Affiliated Hosp, Dept Neurosurg, Luzhou, Sichuan, Peoples R China
[5] Southern Med Univ, TCM Integrated Hosp, Canc Ctr, Guangzhou, Guangdong, Peoples R China
关键词
HUMAN GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMA; NASOPHARYNGEAL CARCINOMA; TUMOR-SUPPRESSOR; EXPRESSION; MICRORNAS; PROLIFERATION; PAKT;
D O I
10.1038/onc.2014.419
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, beta-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.
引用
收藏
页码:4952 / 4963
页数:12
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