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酰基甘油激酶作为一种癌基因和人类胶质瘤的不良预后标志物发挥作用。

Acylglycerol kinase functions as an oncogene and an unfavorable prognostic marker of human gliomas.

作者信息

Liu Nan, Wang Zhen, Cheng Yingduan, Zhang Pengxing, Wang Xin, Yang Hongwei, Liu Hui, Zhang Yongsheng, Tu Yanyang

机构信息

Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

Cipher Ground, North Brunswick, NJ 08902, USA.

出版信息

Hum Pathol. 2016 Dec;58:105-112. doi: 10.1016/j.humpath.2016.07.034. Epub 2016 Aug 27.

Abstract

Acylglycerol kinase (AGK) regulates various cellular processes involved into tumorigenesis and tumor progression. To investigate involvement of AGK in human gliomas, here, quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry analyses were performed to respectively detect the expression of AGK mRNA and protein in glioma and nonneoplastic brain tissue specimens. Then, the associations of AGK expression with various clinicopathological characteristics and patients' prognosis were statistically evaluated. Moreover, the effects of siRNA-mediated AGK knockdown on glioma cell proliferation, migration, and invasion were respectively assessed via Cell Counting Kit-8 and Transwell assays in vitro. As a result, AGK expression, at both mRNA and protein levels, were markedly up-regulated in glioma tissues compared with nonneoplastic brain tissues (both P < .001). In addition, high AGK expression was significantly associated with the grade of malignancy and poor prognosis in glioma patients (all P < .05). Importantly, Cox regression model of multivariate analysis identified AGK expression as an independent prognostic factor for glioma patients (P = .03). Furthermore, silencing the expression of AGK dramatically suppressed cell proliferation, migration, and invasion of glioma cells in vitro (all P < .05). In conclusion, AGK up-regulation may be involved into glioma development and progression, highlighting its prognostic value for the treatment of patients with this malignancy. Further loss-of-function experiments suggest that AGK might play an important role in the viability and motility of glioma cells, implying its potentials as an attractive therapeutic target for this tumor.

摘要

酰基甘油激酶(AGK)调节参与肿瘤发生和肿瘤进展的各种细胞过程。为了研究AGK在人类胶质瘤中的作用,我们进行了定量实时聚合酶链反应、蛋白质免疫印迹和免疫组织化学分析,以分别检测胶质瘤和非肿瘤性脑组织标本中AGK mRNA和蛋白质的表达。然后,对AGK表达与各种临床病理特征及患者预后的相关性进行了统计学评估。此外,通过细胞计数试剂盒-8和体外Transwell实验分别评估了siRNA介导的AGK敲低对胶质瘤细胞增殖、迁移和侵袭的影响。结果显示,与非肿瘤性脑组织相比,胶质瘤组织中AGK在mRNA和蛋白质水平的表达均显著上调(均P <.001)。此外,AGK高表达与胶质瘤患者的恶性程度和预后不良显著相关(均P <.05)。重要的是,多变量分析的Cox回归模型确定AGK表达是胶质瘤患者的独立预后因素(P =.03)。此外,沉默AGK的表达可显著抑制体外胶质瘤细胞的增殖、迁移和侵袭(均P <.05)。总之,AGK上调可能参与胶质瘤的发生和发展,突出了其在这种恶性肿瘤患者治疗中的预后价值。进一步的功能丧失实验表明,AGK可能在胶质瘤细胞的活力和运动中发挥重要作用,暗示其作为这种肿瘤有吸引力的治疗靶点的潜力。

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