WNT4在脑胶质瘤中甲基化下调及抑制恶性胶质瘤细胞增殖的研究

doi:10.11904/j.issn.1002-3070.2020.02.013

Abstract

Abstract: Objective The aims of this study were to investigate the expression and methylation of WNT4 in glioma tissues and malignant glioma cell lines,and its effect and mechanism on the proliferation of glioma U87 cell line.Methods qRT-PCR and Western blot were used to analyze the expression and methylation of WNT4 in human glioma tissues and the expression of WNT4 in U87 cells.MSP was used to analysis the methylation of Wnt4 in glioma tissues.U87 cells were used as experimental cells transfected with lentiviral vectors pLVX-Gfp-WNT4(experimental group)and pLVX-Gfp-NC(control group).Cell proliferation and clone formation experiments were performed to analyze the effect of WNT4A gene on cell proliferation.Western blot was used to verify the effect of WNT4 on the WNT/β-catenin signal pathway.Results Compared with normal human astrocytes,WNT4 mRNA and protein were significantly down-regulated in glioma tissues and cells(P＜0.001).WNT4 methylation was significantly increased in gliomas tissues.The expression of WNT4 was related to the grade of glioma,and the good prognosis of patients with the high expression of WNT4 mRNA;the degree of methylation of WNT4 in glioma tissues was significantly higher than that of normal brain tissues.The Re-expression of WNT4 in significantly decreased in cell viability and proliferation of U87 cells(P＜0.001);The WNT/β-catenin signaling pathway and its downstream cytokines were significantly suppressed after WNT4 expression was restored in U87 cells.Conclusion The expression of WNT4 is down-regulated in human glioma tissues and participates in the progression of gliomas by inhibiting the Wnt/β-catenin signaling pathway.

Key words: Malignant glioma, WNT4,Methylation, Cell proliferation, Wnt/β-catenin

CLC Number:

R793.4

ZHANG Wei, JIANG Xiaodong, CHI Dapeng. WNT4 down-regulates methylation of glioma and inhibits malignant glioma cell proliferation[J]. Journal of Practical Oncology, 2020, 34(2): 156-162.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2020.02.013

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2020/V34/I2/156

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WNT4 down-regulates methylation of glioma and inhibits malignant glioma cell proliferation

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