Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China.
Neoplasma. 2024 Jun;71(3):255-265. doi: 10.4149/neo_2024_240226N80. Epub 2024 May 17.
The most common primary malignant tumor in the adult brain is glioblastoma multiforme (GBM); however, its underlying pathogenic mechanism remains elusive. The never in mitosis (NIMA)-related kinase 2 (NEK2) has been closely associated with the prognosis of various malignancies. Nevertheless, the complete elucidation of NEK2's potential clinical value, particularly in glioma prognosis and development, remains lacking. U87MG and A172 glioblastoma cells were infected with sh-NEK2 lentivirus or oe-NEK2 plasmid to investigate the effect of NEK2 on cell proliferation, migration, and invasion. Cell viability was measured using CCK-8 and colony formation assays, while Transwell assay was utilized to assess cell migration and invasion. Protein expression levels were determined through western blot analysis. Additionally, CGGA and TCGA databases were used for bioinformatics analysis in order to examine the NEK2 expression. Through comprehensive bioinformatics analysis, we identified elevated mRNA expression levels of NEK2 in gliomas compared to normal tissues, which correlated with poor prognosis among glioma patients. Moreover, functional experiments revealed that silencing NEK2 suppressed glioma cell proliferation while overexpression of NEK2 promoted migration and invasion capabilities. Finally, our study uncovered that NEK2 regulates the malignant progression of TP53 wild-type glioblastoma by facilitating TP53 ubiquitination.
成人脑内最常见的原发性恶性肿瘤是多形性胶质母细胞瘤（GBM）；然而，其潜在的发病机制仍难以捉摸。有丝分裂期不可进入（NIMA）相关激酶 2（NEK2）与各种恶性肿瘤的预后密切相关。然而，NEK2 的潜在临床价值，特别是在胶质瘤的预后和发展方面，尚未完全阐明。用 sh-NEK2 慢病毒或 oe-NEK2 质粒感染 U87MG 和 A172 胶质母细胞瘤细胞，以研究 NEK2 对细胞增殖、迁移和侵袭的影响。通过 CCK-8 和集落形成实验测量细胞活力，通过 Transwell 实验评估细胞迁移和侵袭。通过 Western blot 分析测定蛋白表达水平。此外，使用 CGGA 和 TCGA 数据库进行了生物信息学分析，以检查 NEK2 的表达情况。通过综合的生物信息学分析，我们发现与正常组织相比，NEK2 在胶质瘤中的 mRNA 表达水平升高，与胶质瘤患者的不良预后相关。此外，功能实验表明，沉默 NEK2 抑制了胶质瘤细胞的增殖，而过表达 NEK2 则促进了迁移和侵袭能力。最后，我们的研究揭示了 NEK2 通过促进 TP53 泛素化来调节野生型 TP53 胶质母细胞瘤的恶性进展。
