Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis
Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis
复制标题
YB-1敲低对胶质瘤细胞生长、迁移和凋亡的影响及机制
DOI：
10.1093/abbs/gmz161
复制
发表时间：
2020-02-01
影响因子：
3.7
通讯作者：
Zheng, Jin
中科院分区：
文献类型：
--
作者：
Gong, Huilin;Gao, Shan;Zheng, Jin
Y-box结合蛋白1(YB-1)参与细胞的增殖、分化和恶性转化。YB-1的过度表达与胶质瘤的进展和患者的生存有关。本研究旨在研究YB-1基因敲除对胶质瘤细胞生长、迁移和凋亡的影响，揭示YB-1基因敲除对胶质瘤细胞生长、迁移和凋亡的影响机制。研究发现，YB-1基因的敲除降低了U251胶质瘤细胞中YB-1的mRNA和蛋白水平。YB-1基因的敲除显著抑制了细胞的增殖、集落形成、体外迁移和体内肿瘤生长。蛋白质组和磷酸蛋白质组数据显示，YB-1通过调节细胞周期、黏附和凋亡相关主要蛋白的表达和磷酸化，参与了胶质瘤的进展。主要调控蛋白有CCNB1、CCNDBP1、CDK2、CDK3、ADGRG1、CDH-2、MMP14、AIFM1、HO-1和Bax。此外，还发现YB-1基因敲除与癌症中ErbB、mTOR、HIF-1、cGMP-PKG和胰岛素信号通路以及蛋白多糖的低磷酸化有关。我们的研究结果表明，YB-1通过多种方式在胶质瘤的发展中发挥关键作用，包括调节与细胞周期、黏附和凋亡相关的主要蛋白的表达和磷酸化。
Y-box binding protein 1 (YB-1) is manifested as its involvement in cell proliferation and differentiation and malignant cell transformation. Overexpression of YB-1 is associated with glioma progression and patient survival. The aim of this study is to investigate the influence of YB-1 knockdown on glioma cell progression and reveal the mechanisms of YB-1 knockdown on glioma cell growth, migration, and apoptosis. It was found that the knockdown of YB-1 decreased the mRNA and protein levels of YB-1 in U251 glioma cells. The knockdown of YB-1 significantly inhibited cell proliferation, colony formation, and migration in vitro and tumor growth in vivo. Proteome and phosphoproteome data revealed that YB-1 is involved in glioma progression through regulating the expression and phosphorylation of major proteins involved in cell cycle, adhesion, and apoptosis. The main regulated proteins included CCNB1, CCNDBP1, CDK2, CDK3, ADGRG1, CDH-2, MMP14, AIFM1, HO-1, and BAX. Furthermore, it was also found that YB-1 knockdown is associated with the hypo-phosphorylation of ErbB, mTOR, HIF-1, cGMP-PKG, and insulin signaling pathways, and proteoglycans in cancer. Our findings indicated that YB-1 plays a key role in glioma progression in multiple ways, including regulating the expression and phosphorylation of major proteins associated with cell cycle, adhesion, and apoptosis.