MiRNA-451 Inhibits Glioma Cell Proliferation and Invasion Through the mTOR/HIF-1α/VEGF Signaling Pathway by Targeting CAB39

PI3K/AKT/mTOR通路 小RNA 胶质瘤 癌症研究 细胞生长 蛋白激酶B 下调和上调 信号转导 细胞 转染 细胞生物学 生物 细胞培养 基因 遗传学
作者
Nan Yang,Hongbao Guo,Liyun Guo,Le Wang,Bingcheng Ren,Kai Yu,Qiang Huang,Yue Zhong
出处
期刊:Human gene therapy. Clinical development [Mary Ann Liebert, Inc.]
卷期号:29 (3): 156-166 被引量:60
标识
DOI:10.1089/humc.2018.133
摘要

MicroRNAs (miRNAs) are widely expressed and regulate most biological functions. According to several research groups, miR-451 expression is decreased in glioma cells. A previous study also confirmed that miRNA-451 inhibits the PI3K/AKT signaling pathway by directly targeting CAB39, which inhibits glioma cell growth and proliferation and induces apoptosis. However, the specific regulatory mechanism is unclear. Mammalian target of rapamycin (mTOR) is a central regulator of the differentiation, proliferation, and migration of a variety of cells. Hypoxia-inducible factor (HIF)-1α is involved in tumor cell migration and invasion. Close relationships among VEGF overexpression, tumor progression, and poor clinical outcomes have been reported. However, whether miRNA-451 influences glioma cell proliferation and invasion by regulating mTOR, HIF-1α, and VEGF expression remains unknown. This study aimed to assess the effects of miRNA-451 on glioma cell proliferation and invasion in vivo and in vitro by investigating its mechanism. Related gene–protein interactions were also predicted and verified. By targeting CAB39, miRNA-451 likely represses the mTOR/HIF-1α/VEGF pathway to inhibit glioma cell proliferation and invasion. Reverse transcription polymerase chain reaction confirmed that transfection of glioma cells with a lentivirus containing miRNA-451 elevated the expression level of miR-451. Upregulation of miR-451 expression suppressed the growth and invasion of glioma cells in vitro and in vivo by targeting CAB39 and modulating the mTOR/HIF-1α/VEGF signaling pathway. Based on these results, miR-451 suppresses glioma cell proliferation and invasion in vitro and in vivo via suppression of the mTOR/HIF-1α/VEGF signaling pathway by targeting CAB39. Therefore, miR-451 may be a new target for glioma treatment.

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