The expression change of OTUD3-PTEN signaling axis in glioma cells
The expression change of OTUD3-PTEN signaling axis in glioma cells
复制标题
胶质瘤细胞中OTUD3-PTEN信号轴的表达变化
DOI：
10.21037/atm.2020.03.51
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发表时间：
2020-04-01
影响因子：
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通讯作者：
Jiang, Hong
中科院分区：
文献类型：
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作者：
Liu, Yi-Zhen;Du, Xi-Xun;Jiang, Hong
背景含OTU结构域的蛋白3(OTUD3)是卵巢肿瘤蛋白(OTU)家族中的一种去泛素酶(DUB)，已有报道通过OTUD3-PTEN信号轴发挥抗肿瘤作用。胶质瘤是最常见的颅内原发肿瘤，侵袭性高，预后差。虽然不到一半的患者存在10号染色体磷酸酶和张力同源物缺失(PTEN)突变或纯合子缺失，但三分之二的胶质瘤PTEN表达减弱。因此，可以想象，其他未知的机制可能导致PTEN蛋白表达下降。方法在肿瘤基因组图谱数据库(https://www.cancer.gov/))和基因-组织表达数据库(https://commonfund.nih.gov/GTex).)中检测OTUD3在正常组织和脑胶质瘤组织中的表达采用实时荧光定量聚合酶链式反应检测C6细胞和原代星形胶质细胞中OTUD3基因的表达水平。Western印迹法检测C6细胞和原代星形胶质细胞中PTEN和OTUD3蛋白的表达。通过生成Kaplan-Meier曲线，我们预测了OTUD3表达与胶质瘤患者预后之间的关系。结果(1)基于人脑胶质瘤和正常脑标本之间基因表达的微阵列数据，OTUD3在脑胶质瘤中的转录显著下调。(2)C6细胞中OTUD3的表达水平显著低于原代星形胶质细胞。(3)与原代培养的星形胶质细胞相比，C6细胞中PTEN和OTUD3蛋白的表达显著降低。(4)OTUD3高表达的脑胶质瘤患者的生存时间长于低表达的患者。结论OTUD3在胶质瘤中的低表达可能参与了PTEN相关胶质瘤的发生，并可能影响患者的生存。
Background OTU domain-containing protein 3 (OTUD3), as a deubiquitinase (DUB) belonging to the ovarian tumor protease (OTU) family, has been reported to suppress tumor via OTUD3-PTEN signaling axis. Glioma is the most common primary intracranial tumor with high invasiveness and poor prognosis. Although less than half of the patients have phosphatase and tension homologue deleted in chromosome 10 (PTEN) mutations or homozygous deletions, two-thirds of glioma possess diminished PTEN expression. Hence, it is conceivable that other obscure mechanisms may cause the decreased expression of the PTEN protein. Methods OTUD3 expression was assessed in human normal and glioma tissues at The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/) and Genotype-Tissue Expression (GTEx) database (https://commonfund.nih.gov/GTex). The mRNA levels of OTUD3 in C6 cells and primary astrocytes were detected using real-time fluorescence quantitative PCR. Western blot was performed to assay PTEN and OTUD3 protein expression in C6 cells and primary astrocytes. By generating Kaplan-Meier curves, we predicted the association between OTUD3 expression and prognosis in glioma patients. Results (I) OTUD3 transcription was markedly downregulated in glioma based on microarray data for gene expression between human gliomas and normal brain samples. (II) The mRNA levels of OTUD3 in C6 cells was significantly lower than that of in primary astrocytes. (III) The expressions of protein PTEN and OTUD3 in C6 cells were significantly decreased when compared with primary astrocytes. (IV) Glioma patients with high expression of OTUD3 had a longer survival time than patients with low expression. Conclusions Our present findings demonstrated that low expression of OTUD3 in glioma may be involved in PTEN related glioma and may contribute to patient survival.