Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin.
Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin.
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泛素特异性蛋白酶 44 的过度表达通过稳定肿瘤启动子 securin 促进神经胶质瘤的恶性
DOI：
10.18632/oncotarget.16447
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发表时间：
2017-08-29
期刊：
影响因子：
--
通讯作者：
Hu G
中科院分区：
文献类型：
--
作者：
Zou Y;Qiu G;Jiang L;Cai Z;Sun W;Hu H;Lu C;Jin W;Hu G
泛素特异肽酶44(USP44)是纺锤体组装检查点(SAC)的重要组成部分，可防止非整倍体的形成。然而，最近的研究对USP44在肿瘤中的作用提出了争议。在这里，我们首先通过检测几种识别内源性USP44的特异性抗体来证实USP44在核内的定位。免疫组化和定量RT-PCR检测结果显示，USP44在高级别胶质瘤组织中高表达，提示预后不良。USP44基因敲除可抑制已建立的胶质瘤细胞系的增殖、迁移和侵袭，诱导细胞凋亡，使细胞周期停滞于G2/M期。在USP44缺失的细胞中检测到癌蛋白Securin的下调，免疫沉淀证实了内源性USP44与Securin的相互作用，表明Securin是USP44的底物，并可能被USP44稳定。在体内，USP44基因的敲除显著抑制了U87 MG细胞的致瘤性。因此，我们的研究结果表明，USP44的过表达可能通过Securin增强胶质瘤的恶性程度。USP44可能是一个预测性的生物标志物，USP44-Securin通路可能为胶质瘤的治疗提供新的治疗策略。
Ubiquitin specific peptidase 44 (USP44) has been identified as an important component of spindle assemble checkpoint (SAC) to prevent the formation of aneuploidy. However, recent study raised a controversy about the effect of USP44 in tumor. Here, we first confirmed the intranuclear localization of USP44 by testing several specific antibodies to recognize endogenous USP44. Then, data from IHC and qRT-PCR assay indicated that the high expression of USP44 existed in high-grade glioma tissues and signified a poor prognosis. Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines. Down-regulation of oncoprotein securin was detected in USP44 deficient cells, and the interaction of endogenous USP44 and securin was confirmed by immunoprecipitation in U251MG cells, which indicated that securin was a substrate of USP44, and might be stabilized by USP44. In vivo, knockdown of USP44 inhibited the tumorigenicity of U87MG cells significantly. Consequently, our findings suggested that overexpression of USP44 could enhance the malignancy of glioma via securin. USP44 might serve as a predictive biomarker, and the USP44-securin pathway might provide a new therapeutic strategy for the treatment of glioma.