Department of Neurosurgery, Linyi People's Hospital, Linyi, 276000, Shandong Province, People's Republic of China.
Department of Neurosurgery, Qingdao University, Qingdao, 266071, Shandong Province, People's Republic of China.
J Mol Neurosci. 2019 Dec;69(4):527-537. doi: 10.1007/s12031-019-01355-3. Epub 2019 Aug 3.
Cut-like homeobox-1 (CUX1) is expressed in the upper layer of the cortex and participates in DNA replication, cell cycle control, and DNA repair. It has been shown to be involved in the proliferation of various types of solid tumors. The aims of this study were to explore the relationship between CUX1 expression and the prognosis of glioma by performing a series of functional experiments and bioinformatic analyses. Firstly, we found that CUX1 expression levels differed among patients with different grades of gliomas, and they were significantly correlated with the prognosis of glioma patients according to an analysis of data from a public database. qRT-PCR, western blotting, and immunohistochemical analysis of CUX1 were performed to demonstrate that the expression of CUX1 was positively correlated with the glioma WHO grade (P < 0.05) and several malignant clinical pathological parameters, including Ki67 and P53mut. In addition, the multivariate Cox regression and Kaplan-Meier curves showed that CUX1 expression exerted predictive value for overall survival. Finally, to further investigate the functions of CUX1, we identified CUX1-associated genes and, though GO/KEGG analysis, their associated biological functions and signaling pathways; the results suggested that the activity of CUX1 might be exerted via the JAK-STAT pathway or other key regulators of the cell cycle to promote proliferation, inflammation, and chemotherapy resistance in glioma. Taken together, these results indicate that CUX1 is a potential biomarker of malignancy and prognosis and may serve as a potential therapeutic target for glioma patients.
剪状同源盒蛋白 1（CUX1）在上皮层表达，参与 DNA 复制、细胞周期调控和 DNA 修复。它已被证明参与各种实体肿瘤的增殖。本研究旨在通过一系列功能实验和生物信息学分析，探讨 CUX1 表达与胶质瘤预后的关系。首先，我们发现 CUX1 的表达水平在不同级别胶质瘤患者之间存在差异，根据公共数据库数据分析，它们与胶质瘤患者的预后显著相关。通过 qRT-PCR、western blot 和 CUX1 免疫组化分析，证明 CUX1 的表达与胶质瘤 WHO 分级呈正相关（P<0.05），与 Ki67 和 P53mut 等几种恶性临床病理参数也呈正相关。此外，多变量 Cox 回归和 Kaplan-Meier 曲线表明 CUX1 表达对总生存期具有预测价值。最后，为了进一步研究 CUX1 的功能，我们鉴定了与 CUX1 相关的基因，并通过 GO/KEGG 分析，确定了它们相关的生物学功能和信号通路；结果表明，CUX1 的活性可能通过 JAK-STAT 通路或细胞周期的其他关键调节因子发挥作用，从而促进胶质瘤的增殖、炎症和化疗耐药性。总之，这些结果表明 CUX1 是一种潜在的恶性肿瘤和预后生物标志物，可能成为胶质瘤患者的潜在治疗靶点。
