Xu Li, Li Jinquan, Bao Zhen, Xu Peng, Chang Hao, Wu Jingjing, Bei Yuanqi, Xia Liuwan, Wu Peizhang, Yan Ke, Lu Bing, Cui Gang
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong, Jiangsu Province, China.
Neuropathology. 2017 Jun;37(3):217-226. doi: 10.1111/neup.12366. Epub 2017 Jan 31.
OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0.05). Moreover, Kaplan-Meier curve also indicated that high expression of OTUB1 was correlated with a poor prognosis. In vitro, silencing OTUB1 retarded the migration ability of glioma cells. Knockdown of OTUB1 increases epithelial-mesenchymal transition-related protein E-cadherin expression, but decreases simultaneously the expression of vimentin and snail. Furthermore, down-regulated expression of OTUB1 also resulted in decreased expression of some extracellular matrix degradation-related proteins, such as matrix metallopeptidase (MMP)2 and MMP9. All results suggested that OTUB1 was a valuable marker in the pathogenesis of human gliomas and could be used as a novel biomarker for glioma therapy in the future.
含OTU结构域的泛素醛结合蛋白1（OTUB1）是一种属于卵巢肿瘤（OTU）家族的去泛素化酶（DUB），据报道与多种恶性肿瘤的发生发展有关。然而，OTUB1在人类胶质瘤中的潜在功能仍不清楚。在本研究中，我们试图探讨OTUB1在胶质瘤病理过程中的作用，并分析其相关的临床意义。蛋白质免疫印迹法和免疫组织化学分析表明，OTUB1在胶质瘤组织中高表达，统计分析表明OTUB1的表达水平与人类胶质瘤的WHO分级显著相关（P<0.05）。此外，Kaplan-Meier曲线也表明OTUB1的高表达与预后不良相关。在体外，沉默OTUB1可抑制胶质瘤细胞的迁移能力。敲低OTUB1可增加上皮-间质转化相关蛋白E-钙黏蛋白的表达，但同时降低波形蛋白和蜗牛蛋白的表达。此外，OTUB1表达下调还导致一些细胞外基质降解相关蛋白的表达降低，如基质金属蛋白酶（MMP）2和MMP9。所有结果表明，OTUB1是人类胶质瘤发病机制中的一个有价值的标志物，未来可作为胶质瘤治疗的新型生物标志物。
