胶质母细胞瘤（GBM）是颅内胶质瘤中最具侵袭性的。尽管采取了最大程度的治疗干预，中位生存率仍然约为 14-16 个月。核受体结合蛋白1（NRBP1）对细胞的生物学功能具有潜在的生长促进作用。在本研究中，我们探讨了NRBP1是否促进GBM恶性表型及其潜在机制。分析了TCGA/CGGA数据库中NRBP1与胶质瘤分级、预后的相关性以及我们的临床数据。接下来，我们对GBM细胞进行NRBP1的敲除和过表达，以验证NRBP1在体外和体内促进细胞增殖、侵袭和迁移。最后，我们检测了 NRBP1 对 PI3K/Akt 信号通路和 EMT 的影响。NRBP1 表达升高与晚期胶质瘤以及总体生存率和无病生存率降低之间存在相关性。 NRBP1 敲除后观察到肿瘤细胞的增殖、侵袭和迁移受到抑制，体外研究还证明了细胞凋亡的诱导。然而，其过度表达与高增殖率、迁移、侵袭和凋亡逃逸相关。 GO富集和KEGG分析显示NRBP1调控的差异表达基因簇参与PI3K/Akt信号通路以及该通路介导的EMT。此外，MK-2206 和 SC79 减轻了 NRBP1 敲低和过表达对 GBM 的影响，两者分别充当 PI3K/Akt 信号通路的抑制剂和激活剂。同样，在小鼠模型中，NRBP1 的抑制导致肿瘤生长减少，而其过度表达则促进肿瘤生长。这项研究表明，NRBP1 通过激活 PI3K/Akt 通路促进 GBM 的恶性表型。因此，它既可以作为 GBM 治疗的预测指标，也可以作为治疗的新靶标。© 2024 作者。约翰·威利出版的癌症医学

Glioblastoma (GBM) is the most aggressive of intracranial gliomas. Despite the maximal treatment intervention, the median survival rate is still about 14-16 months. Nuclear receptor-binding protein 1 (NRBP1) has a potential growth-promoting role on biology function of cells. In this study, we investigated whether NRBP1 promotes GBM malignant phenotypes and the potential mechanisms.The correlation between NRBP1 and glioma grade, prognosis in TCGA/CGGA databases and our clinical data were analyzed. Next, we conducted knockout and overexpression of NRBP1 on GBM cells to verify that NRBP1 promoted cell proliferation, invasion, and migration in vitro and in vivo. Finally, we detected the impact of NRBP1 on PI3K/Akt signaling pathway and EMT.There was a correlation between elevated NRBP1 expression and advanced stage glioma, as well as decreased overall and disease-free survival. The suppression of proliferation, invasion, and migration of tumor cells was observed upon NRBP1 knockout, and in vitro studies also demonstrated the induction of apoptotic cell death. Whereas, its overexpression is associated with high multiplication rate, migration, invasion, and apoptotic escape. GO enrichment and KEGG analysis revealed that NRBP1 regulated differentially expressed gene clusters are involved in PI3K/Akt signaling pathway, as well as EMT mediated by this pathway. Moreover, the effects of NRBP1 knockdown and overexpression on GBM were mitigated by MK-2206 and SC79, both of which respectively function as an inhibitor and an activator of the PI3K/Akt signaling pathway. Similarly, the suppression of NRBP1 led to a decrease in tumor growth, whereas its overexpression promoted tumor growth in a mouse model.This study shows that NRBP1 promotes malignant phenotypes in GBM by activating PI3K/Akt pathway. Hence, it can function as both a predictive indicator and a new target for therapies in GBM treatment.© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.