Geng Yibo, Xu Cheng, Wang Yi, Zhang Liwei
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
China National Clinical Research Center for Neurological Disease, Beijing, People's Republic of China.
Onco Targets Ther. 2020 Jun 17;13:5721-5729. doi: 10.2147/OTT.S255941. eCollection 2020.
Quiescin sulfhydryl oxidase 1 (QSOX1) involves in the formation of disulfide bonds and participates in the protein folding process. In recent years, accumulating evidences have shown that QSOX1 is a biomarker for tumor development and prognosis. However, the biological function of QSOX1 in glioblastoma (GBM) remains unclear.
QSOX1 expression in glioma and overall survival of glioma patients were analyzed through The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. shRNAs were used to decrease the expression of QSOX1 in U87 and U251 cells. Celltiter-Glo and colony formation assays were used to assess cell proliferation. Transwell and scratch assays were utilized to determine cell migration and invasion, the xenograft mouse models were established to evaluate the effect of QSOX1 knockdown in vivo. Western blot assays were used to detect the changes of E-cadherin/N-cadherin/vimentin and PI3K/Akt pathway.
We found that QSOX1 was upregulated in glioma, especially in GBM. Upregulation of QSOX1 was correlated with poor prognosis in glioma patients. We discovered for the first time that suppression of QSOX1 expression inhibited proliferation, migration and invasion, as well as epithelial-mesenchymal transition (EMT) in GBM cell lines. In addition, phosphorylated PI3K and Akt were downregulated in the QSOX1-knockdown groups. Moreover, QSOX1 knockdown-impaired cell growth was partially rescued by Akt activator.
Our findings revealed that QSOX1 was a novel biomarker for GBM patients and QSOX1 promoted cell proliferation, migration and invasion through regulating PI3K/Akt pathway in GBM.
巯基氧化酶1（QSOX1）参与二硫键的形成并参与蛋白质折叠过程。近年来，越来越多的证据表明QSOX1是肿瘤发生发展和预后的生物标志物。然而，QSOX1在胶质母细胞瘤（GBM）中的生物学功能仍不清楚。
通过癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库分析QSOX1在胶质瘤中的表达及胶质瘤患者的总生存期。使用短发夹RNA（shRNAs）降低U87和U251细胞中QSOX1的表达。采用Celltiter-Glo和集落形成试验评估细胞增殖。利用Transwell和划痕试验测定细胞迁移和侵袭能力，建立异种移植小鼠模型以评估体内敲低QSOX1的效果。采用蛋白质免疫印迹法检测E-钙黏蛋白/N-钙黏蛋白/波形蛋白和PI3K/Akt信号通路的变化。
我们发现QSOX1在胶质瘤中上调，尤其是在GBM中。QSOX1的上调与胶质瘤患者的不良预后相关。我们首次发现抑制QSOX1表达可抑制GBM细胞系的增殖、迁移和侵袭以及上皮-间质转化（EMT）。此外，在QSOX1敲低组中磷酸化的PI3K和Akt下调。而且，Akt激活剂部分挽救了QSOX1敲低导致的细胞生长受损。
我们的研究结果表明，QSOX1是GBM患者的一种新型生物标志物，并且QSOX1通过调节GBM中的PI3K/Akt信号通路促进细胞增殖、迁移和侵袭。
