Regulation of Glioma Cells Migration by DYRK2

Regulation of Glioma Cells Migration by DYRK2
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DYRK2 对神经胶质瘤细胞迁移的调节

DOI:
10.1007/s11064-017-2345-2
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发表时间:
2017
影响因子:
4.4
通讯作者:
Cheng Chun
Cheng Chun
中科院分区:
医学3区
文献类型:
--
作者:
Shen Yifen;Zhang Li;Wang Donglin;Bao Yifeng;Liu Chao;Xu Zhiwei;Huang Wei;Cheng Chun

文献摘要

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双特异性酪氨酸调节激酶2(DYRK 2)是一种磷酸化丝氨酸/苏氨酸底物的蛋白激酶,在许多人类肿瘤中表达,但对其在胶质瘤病理生理学中的作用知之甚少。本研究旨在探讨其在人脑胶质瘤中的表达及功能。采用免疫印迹和免疫组化方法检测84例脑胶质瘤组织中DYRK 2蛋白的表达。通过伤口愈合实验和transwell实验检测细胞迁移能力。我们发现,DYRK 2的水平在高级别胶质瘤组织中与低级别组织相比显著降低。DYRK 2的表达水平与胶质瘤病理分级和E-cadherin表达呈正相关。Kaplane-Meier分析显示DYRK 2低表达与胶质瘤患者预后不良有关。创伤愈合实验和transwell实验表明,DYRK 2可通过PI 3 K/AKT/GSK 3 β信号通路抑制细胞迁移,并影响E-cadherin和vimentin的表达。因此,DYRK 2可能成为胶质瘤的一个潜在治疗靶点,同时也是一个有前景的预后生物标志物。
Dual-specificity tyrosine-regulated kinase 2 (DYRK2), a protein kinase that phosphorylates its substrates on serine/threonine, is expressed in numerous human tumors, but little is known about its role in the pathophysiology of glioma. In this study, we made an effort to explore the expression and function in human glioma. Western blot and immunohistochemistry analysis were performed to investigate the expression of DYRK2 protein in glioma tissues in 84 patients. Wound healing and transwell assay were carried out to determine the cell migration ability. We showed that the level of DYRK2 was significantly decreased in high-grade glioma tissues compared with low-grade tissues. In addition, the expression level of DYRK2 was positively correlated with glioma pathological grade and E-cadherin expression. Kaplane–Meier analysis revealed that low expression of DYRK2 was related to poor prognosis of glioma patients. Furthermore, wound healing and transwell assay revealed that DYRK2 could suppress cell migration and affect the expression levels of E-cadherin and vimentin through PI3K/AKT/GSK3β signaling pathway. Taken together, our results implied that DYRK2 could serve as a promising prognostic biomarker as well as a potential therapeutical target of glioma.