Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Oncol Rep. 2019 Sep;42(3):963-972. doi: 10.3892/or.2019.7227. Epub 2019 Jul 10.
Glioblastoma (GBM) is the most common primary intracranial malignancy. GBM still exhibits high recurrence and mortality rates even following combined treatment with surgery, radiotherapy and chemotherapy, Therefore, the identification of novel therapeutic targets is urgent. Previous research has shown that nicotinamide phosphoribosyltransferase (NAMPT) plays a key role in cell metabolism and is closely related to the occurrence and development of many tumor types; yet, little is known concerning its relationship with GBM. Oncomine database analysis showed that the expression of NAMPT in GBM was higher than that in normal tissues; this finding was further confirmed by immunohistochemical staining of a tissue microarray. Data analysis with the R2 platform showed that patients with higher expression of NAMPT had worse prognoses than those with lower NAMPT expression. Using the GBM data in TCGA, four pathways enriched in the high NAMPT expression group were identified by gene set enrichment analysis (GSEA). NAMPT expression was knocked down in U87 and U251 GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting NAMPT. CCK‑8, colony formation, wound healing, Transwell and apoptosis assays were carried out. The results showed that NAMPT knockdown decreased cell proliferation, migration, and invasion and promoted apoptosis. U87 GBM cells were used in a model of subcutaneous tumorigenesis in nude mice. The results showed that NAMPT knockdown slowed the growth of tumors in vivo. Therefore, we speculate that NAMPT may be a potential prognostic and therapeutic biomarker for glioblastoma.
胶质母细胞瘤（GBM）是最常见的原发性颅内恶性肿瘤。即使在手术、放疗和化疗联合治疗后，GBM 仍表现出高复发率和死亡率。因此，迫切需要确定新的治疗靶点。先前的研究表明，烟酰胺磷酸核糖转移酶（NAMPT）在细胞代谢中起关键作用，与许多肿瘤类型的发生和发展密切相关；然而，其与 GBM 的关系知之甚少。Oncomine 数据库分析显示，GBM 中 NAMPT 的表达高于正常组织；组织微阵列免疫组化染色进一步证实了这一发现。R2 平台数据分析显示，NAMPT 表达较高的患者预后比 NAMPT 表达较低的患者差。使用 TCGA 的 GBM 数据，通过基因集富集分析（GSEA）鉴定了高 NAMPT 表达组中富集的四个途径。通过携带靶向 NAMPT 的短发夹 RNA（shRNA）的慢病毒载体敲低 U87 和 U251 GBM 细胞中的 NAMPT。进行 CCK-8、集落形成、划痕愈合、Transwell 和凋亡测定。结果表明，NAMPT 敲低降低了细胞增殖、迁移和侵袭，并促进了细胞凋亡。将 U87 GBM 细胞用于裸鼠皮下肿瘤发生模型。结果表明，NAMPT 敲低减缓了体内肿瘤的生长。因此，我们推测 NAMPT 可能是胶质母细胞瘤潜在的预后和治疗生物标志物。
