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泛素特异性蛋白酶15促进胶质母细胞瘤中肿瘤细胞的侵袭和增殖。

Ubiquitin-specific protease 15 promotes tumor cell invasion and proliferation in glioblastoma.

作者信息

Xu Ke, Pei Hua, Zhang Zhenhao, Wang Huamin, Li Liang, Xia Qianfeng

机构信息

Department of Immunology, School of Tropical and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571101, P.R. China.

Medical Technology Institute of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.

出版信息

Oncol Lett. 2018 Mar;15(3):3846-3851. doi: 10.3892/ol.2018.7747. Epub 2018 Jan 8.

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor worldwide. Despite the advances made in treatment and research, the median survival time for GBM patients remains <1.5 years, providing impetus for the identification of potential novel therapeutic target genes to improve GBM treatment. The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15) has emerged as a pro-oncogenic factor; however, its function in GBM has yet to be fully elucidated. The present study sought to determine whether or not USP15 is implicated in GBM cell invasion and proliferation. Following the depletion of USP15 in U87-MG and U251-MG cells by lentivirus-mediated USP15 short hairpin RNA (shRNA), the invasiveness of glioma cells was investigated. The results of the present study demonstrated that glioma cells expressing USP15 shRNA exhibited significantly lower invasiveness than cells that did not express USP15 shRNA. Additionally, USP15 depletion led to the upregulation of E-cadherin and downregulation of the mesenchymal markers, N-cadherin and vimentin. Furthermore, the influence of USP15 on glioma cell proliferation was investigated and depletion of USP15 resulted in a marked reduction in cell proliferation. Taken together, the findings of the present study clearly support the hypothesis that USP15 renders GBM cells capable of invasion and proliferation.

摘要

多形性胶质母细胞瘤(GBM)是全球最具侵袭性的脑肿瘤类型之一。尽管在治疗和研究方面取得了进展,但GBM患者的中位生存时间仍小于1.5年,这为鉴定潜在的新型治疗靶基因以改善GBM治疗提供了动力。去泛素化酶泛素特异性肽酶15(USP15)已成为一种促癌因子;然而,其在GBM中的功能尚未完全阐明。本研究旨在确定USP15是否与GBM细胞的侵袭和增殖有关。通过慢病毒介导的USP15短发夹RNA(shRNA)使U87-MG和U251-MG细胞中的USP15缺失后,研究了胶质瘤细胞的侵袭性。本研究结果表明,表达USP15 shRNA的胶质瘤细胞的侵袭性明显低于未表达USP15 shRNA的细胞。此外,USP15缺失导致E-钙黏蛋白上调,间充质标志物N-钙黏蛋白和波形蛋白下调。此外,研究了USP15对胶质瘤细胞增殖的影响,USP15缺失导致细胞增殖显著减少。综上所述,本研究结果明确支持USP15使GBM细胞具有侵袭和增殖能力这一假说。

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