The Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
School of Graduate Studies, Wannan Medical College, Wuhu, Anhui, China.
Mol Cancer Res. 2023 Mar 1;21(3):189-198. doi: 10.1158/1541-7786.MCR-22-0504.
Our previous study illustrated that nuclear factor IX (NFIX) promotes glioblastoma (GBM) progression by inducing migration and proliferation of GBM cells. However, the underlying mechanism of how NFIX regulates GBM cell proliferation remains obscure. In this study, we uncovered that Go-Ichi-Ni-San 1 (GINS1) is upregulated and positively correlated with NFIX in human GBM specimen. NFIX silencing downregulates the expression of GINS1, which is pivotal for cell-cycle progression and proliferation of GBM cells. Replenishment of GINS1 largely rescues the NFIX-null effect on GBM cell proliferation. Mechanistic investigation revealed that NFIX transcriptionally actives GINS1 expression by directly binding to promoter region (-1779 to -1793bp) of the GINS1 gene. Furthermore, knockdown of NFIX sensitizes GBM cells to DNA damage-inducing agents including doxorubicin and temozolomide, in a GINS1-dependent manner.
Our study highlights that targeting NFIX-GINS1 axis could be a novel and potential therapeutic approach for GBM treatment.
我们之前的研究表明，核因子 IX（NFIX）通过诱导脑胶质瘤（GBM）细胞的迁移和增殖来促进 GBM 的进展。然而，NFIX 如何调节 GBM 细胞增殖的潜在机制仍不清楚。在这项研究中，我们发现 Go-Ichi-Ni-San 1（GINS1）在人 GBM 标本中上调，并与 NFIX 呈正相关。NFIX 沉默下调 GINS1 的表达，GINS1 对于 GBM 细胞的细胞周期进程和增殖至关重要。补充 GINS1 可在很大程度上挽救 NFIX 缺失对 GBM 细胞增殖的影响。机制研究表明，NFIX 通过直接结合 GINS1 基因的启动子区域（-1779 至-1793bp）转录激活 GINS1 的表达。此外，NFIX 的敲低以 GINS1 依赖的方式使 GBM 细胞对包括阿霉素和替莫唑胺在内的 DNA 损伤诱导剂敏感。
我们的研究强调，针对 NFIX-GINS1 轴可能是治疗 GBM 的一种新的潜在治疗方法。
