Upregulation of p72 Enhances Malignant Migration and Invasion of Glioma Cells by Repressing Beclin1 Expression

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Zhenxing Zhang¹, He Tian², Ye Miao¹, Xu Feng¹, Yang Li¹, Honglei Wang¹, and Xiaofeng Song^2*

¹Liaoning Medical University, Department of Neurosurgery, 121001 Jinzhou, China

²Liaoning Medical University, Department of Histology and Embryology, 121001 Jinzhou, China; E-mail: Songzhenxing151121@163.com

^* To whom correspondence should be addressed.

Received November 21, 2015; Revision received February 21, 2016

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p72 is the member of the DEAD-box RNA helicase family, which can unwind double-stranded RNA and is efficient for microRNA (miRNA, miR) processing. However, its specific role in glioma has not been elucidated. First, the expression of p72 in glioma cell lines and tissues was explored using Western blot. To explore the role of p72 on glioma progression, adenovirus inhibiting p72 was transfected into A172 and T98G cells. Cell autophagy was determined using GFP-LC3 dots, and cell apoptosis was determined using flow cytometry. The effect of Beclin1 was explored using GFP-LC3 dots, flow cytometry, and colony formation. The possible miRNAs that target the 3′-untranslated region (3′-UTR) of Beclin1 were predicted using TargetScan. Dual luciferase reporter assay was applied to determine whether these miRNAs bind to the 3′-UTR of Beclin1. The expression of p72 was significantly increased in glioma cell lines and tissues. Autophagy-related protein Beclin1 was found to be significantly enhanced when p72 was inhibited. The accumulation of GFP-LC3 dots was significant in cells transfected with ad-sh-p72 compared with ad-con. Colony formation capacity and cell apoptosis were also found to be significantly decreased with p72 inhibition. Furthermore, upregulation of Beclin1 contributes to A172 cell autophagy, invasion, and apoptosis. Overexpression of p72 induces increased miR-34-5p and miR-5195-3p expression in A172 and T98G cells. Beclin1 was the target gene of miR-34-5p and miR-5195-3p. In conclusion, we found for the first time that overexpression of p72 decreased Beclin1 expression partially by increasing miR-34-5p and miR-5195-3p expression in A172 and T98G cells.

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KEY WORDS: glioma, p72, miR-34-5p, miR-5195-3p, Beclin1

DOI: 10.1134/S0006297916060031

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