Gao Hua-Song, Lin She-Yu, Han Xi, Xu Hong-Zhi, Gao Yi-Lu, Qin Zhi-Yong
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Biological Sciences, School of Life Sciences, Nantong University, Nantong, China.
Ann Transl Med. 2021 Apr;9(8):659. doi: 10.21037/atm-21-935.
Glioma is a type of tumor that usually occurs in the adult central nervous system. Protein kinases have become important targets for oncotherapy since they are closely correlated with signal transduction. The role of the casein kinase 1 (CK1) gene in glioma remains to be fully elucidated.
The mRNA and protein expression of CK1 were analyzed by Realtime PCR, Western blot and immunohistochemistry. The cell behavior was assayed by MTT, Transwell and cell scratch methods. Cell cycle and cell apoptosis were performed by flow cytometer. Construction of stable cell line was completed by lentivirus infection. The nude mouse model was used for analysis on the role of CK1 by injecting the cells into subcutaneous tissue, tail vein and cerebral cortex. The prognostic role of CK1 in glioma was evaluated using Kaplan-Meier and Cox regression analyses.
immunohistochemical staining demonstrated that the expression of CK1 in glioma samples was correlated with the grade of glioma. Survival analysis using Kaplan-Meier and multivariate analysis by Cox regression indicated that CK1 could be used as an independent prognostic marker for glioma. The methyl thiazolyl tetrazolium (MTT), transwell, and cell scratch assays demonstrated that the CK1 gene promoted cell proliferation and invasion through the phosphatidylinositol 3 kinase/matrix metalloproteinase 2 (AKT-MMP2) signaling pathway. experiments in mice also confirmed the ability of CK1 to enhance tumor proliferation and metastasis, with the metastatic site being the small intestine.
the expression of CK1 was correlated with glioma grade and patient survival and it may enhance glioma proliferation and metastasis via AKT-MMP2 pathway.
胶质瘤是一种通常发生于成人中枢神经系统的肿瘤类型。蛋白激酶由于与信号转导密切相关,已成为肿瘤治疗的重要靶点。酪蛋白激酶1(CK1)基因在胶质瘤中的作用仍有待充分阐明。
通过实时定量聚合酶链反应(Realtime PCR)、蛋白质免疫印迹法(Western blot)和免疫组织化学法分析CK1的mRNA和蛋白表达。采用MTT法、Transwell法和细胞划痕法检测细胞行为。通过流式细胞仪检测细胞周期和细胞凋亡。通过慢病毒感染构建稳定细胞系。将细胞注射到皮下组织、尾静脉和大脑皮层,利用裸鼠模型分析CK1的作用。使用Kaplan-Meier法和Cox回归分析评估CK1在胶质瘤中的预后作用。
免疫组织化学染色显示,CK1在胶质瘤样本中的表达与胶质瘤分级相关。使用Kaplan-Meier法进行生存分析以及Cox回归多因素分析表明,CK1可作为胶质瘤的独立预后标志物。MTT法、Transwell法和细胞划痕试验表明,CK1基因通过磷脂酰肌醇3激酶/基质金属蛋白酶2(AKT-MMP2)信号通路促进细胞增殖和侵袭。小鼠实验也证实了CK1增强肿瘤增殖和转移的能力,转移部位为小肠。
CK1的表达与胶质瘤分级及患者生存相关,并且它可能通过AKT-MMP2通路增强胶质瘤的增殖和转移。