Journal
HUMAN GENE THERAPY CLINICAL DEVELOPMENT
Volume 29, Issue 3, Pages 156-166Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/humc.2018.133
Keywords
glioma; miRNA-451; CAB39; mTOR; HIF-1 alpha; VEGF
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Funding
- National Natural Science Foundation of China [81572490]
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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)-1 alpha 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-1 alpha, 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-1 alpha/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 miR451 expression suppressed the growth and invasion of glioma cells in vitro and in vivo by targeting CAB39 and modulating the mTOR/HIF-1 alpha/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-1 alpha/VEGF signaling pathway by targeting CAB39. Therefore, miR-451 may be a new target for glioma treatment.
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