Yang Hui, Liu Xiaocen, Zhu Xiaolong, Zhang Mengying, Wang Yingying, Ma Mingzhe, Lv Kun
Department of Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241001, China.
Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu 241001, China.
iScience. 2022 Aug 17;25(9):104952. doi: 10.1016/j.isci.2022.104952. eCollection 2022 Sep 16.
GINS1 is a GINS complex subunit that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Despite the significance of the GINS complex in the switch between quiescence and proliferation of glioma cells inside and outside the perinecrotic niche, the biological functions and the underlying mechanism of GINS1 remain unclear. Unlike in normal cells and tissues, GINS1 expression level was significantly upregulated in glioma cells and tissues. High expression of GINS1 predicted an advanced clinical grade and a poor survival. Functional assays revealed that GINS1 aggravated glioma malignant phenotypes and . Mechanistically, this study identified that GINS1 physically interacts with TOP2A. GINS1 promotes glioma cell proliferation and migration through USP15-mediated deubiquitination of TOP2A protein. Our results delineate the clinical significance of GINS1 in glioma and the regulatory mechanisms involved in glioma cell proliferation and migration. This work provides potential therapeutic targets for glioma treatment.
GINS1是一种GINS复合物亚基，在真核生物DNA复制中与MCM2-7复合物和Cdc45协同发挥作用。尽管GINS复合物在坏死周围微环境内外的胶质瘤细胞静止与增殖转换中具有重要意义，但GINS1的生物学功能及其潜在机制仍不清楚。与正常细胞和组织不同，GINS1在胶质瘤细胞和组织中的表达水平显著上调。GINS1的高表达预示着临床分级较高且生存期较差。功能实验表明，GINS1加剧了胶质瘤的恶性表型。从机制上讲，本研究发现GINS1与TOP2A存在物理相互作用。GINS1通过USP15介导的TOP2A蛋白去泛素化促进胶质瘤细胞增殖和迁移。我们的结果阐明了GINS1在胶质瘤中的临床意义以及胶质瘤细胞增殖和迁移所涉及的调控机制。这项工作为胶质瘤治疗提供了潜在的治疗靶点。
