GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway
GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway
复制标题
GOLM1 沉默通过 Wnt/β-catenin 信号通路抑制人胶质母细胞瘤细胞的增殖和运动
DOI：
10.1016/j.brainres.2019.03.035
复制
发表时间：
2019-08-15
期刊：
影响因子：
2.9
通讯作者：
Chen, Qianxue
中科院分区：
文献类型：
--
作者：
Ding, Xiang;Deng, Gang;Chen, Qianxue
高尔基体膜蛋白1(GOLM1)是一种II型跨膜蛋白，定位于顺行和内侧高尔基体。由于其作为癌基因和原蛋白转换酶(PC)共识位点的功能，GOLM1将在基因靶向治疗中发挥重要作用，并作为候选的肿瘤生物标记物。然而，很少有研究探讨其与胶质母细胞瘤(GBM)进展的相关性。本研究检测了临床GBM组织中GOLM1mRNA和蛋白的过度表达。用酶联免疫吸附试验检测，GBM患者血清中分泌的GOLM1水平也异常升高。然后，我们利用小干扰RNA(SiRNAs)沉默GOLM1在GBM U87和U251细胞中的表达。沉默GOLM1表达后，细胞增殖下降，细胞周期停滞于G1/S期，肿瘤细胞运动也受到抑制。此外，增殖相关蛋白和上皮-间充质转化(EMT)相关标志物的水平也发生了变化。此外，Wnt/β-catenin信号通路受到显著抑制，尤其是β-catenin的核转位。GOLM1基因的敲除也抑制了裸鼠模型中移植瘤的生长。GOLM1通过促进细胞的增殖、迁移和侵袭，在GBM中扮演着关键的癌基因的角色。其作用机制可能与Wnt/β-catenin信号通路有关。GOLM1还显示出作为GBM生物标志物的巨大潜力。
Golgi membrane protein 1 (GOLM1) is a type II transmembrane protein located in the cis- and medial-Golgi. Due to its function as an oncogene and proprotein convertase (PC) consensus site, GOLM1 will play a vital role in gene-targeted therapies and serve as a candidate tumor biomarker. However, few studies have explored its correlation with glioblastoma (GBM) progression. In this study, we detected the overexpression of the GOLM1 mRNA and protein in clinical GBM samples. The level of secreted GOLM1 in the serum from patients with GBM was also abnormally elevated, as determined by an Elisa. Then we utilized small interfering RNAs (siRNAs) to silence GOLM1 expression in GBM U87 and U251 cells. After silencing GOLM1 expression, the proliferation of cells decreased, the cell cycle was arrested in G1/S phase, and tumor cell motility was also inhibited. Moreover, the levels of proliferation-associated proteins and epithelial-mesenchymal transition (EMT)-related markers were also altered. Additionally, the Wnt/beta-catenin signaling pathway was significantly suppressed, particularly the nuclear translocation of beta-catenin. Knockdown of GOLM1 also inhibits xenograft tumor growth in nude mouse models.GOLM1 acts as a critical oncogene in GBM by promoting cell proliferation, migration and invasion. Its mechanism may be related to the Wnt/beta-catenin signaling pathway. GOLM1 also exhibits great potential as a biomarker for GBM.