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DYRK2 对神经胶质瘤细胞迁移的调控

Regulation of Glioma Cells Migration by DYRK2.

机构信息

Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People's Republic of China.

Department of Pathogen, Medical College, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People's Republic of China.

出版信息

Neurochem Res. 2017 Nov;42(11):3093-3102. doi: 10.1007/s11064-017-2345-2. Epub 2017 Jul 4.

Abstract

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.

摘要

双特异性酪氨酸磷酸化调节激酶 2(DYRK2)是一种能够在丝氨酸/苏氨酸残基上磷酸化其底物的蛋白激酶,在许多人类肿瘤中表达,但对其在神经胶质瘤病理生理学中的作用知之甚少。在这项研究中,我们努力探讨其在人类神经胶质瘤中的表达和功能。通过 Western blot 和免疫组织化学分析,检测 84 例患者的神经胶质瘤组织中 DYRK2 蛋白的表达。通过划痕愈合和 Transwell 实验来确定细胞迁移能力。我们发现,与低级别组织相比,高级别神经胶质瘤组织中 DYRK2 的水平显著降低。此外,DYRK2 的表达水平与神经胶质瘤的病理分级和 E-钙黏蛋白表达呈正相关。Kaplane-Meier 分析显示,DYRK2 低表达与神经胶质瘤患者预后不良有关。此外,划痕愈合和 Transwell 实验表明,DYRK2 通过 PI3K/AKT/GSK3β 信号通路抑制细胞迁移,并影响 E-钙黏蛋白和波形蛋白的表达水平。综上所述,我们的研究结果表明,DYRK2 可以作为神经胶质瘤有前途的预后生物标志物和潜在的治疗靶点。

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