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Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin

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...

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Autores principales: Zou, Yongxiang, Qiu, Guanzhong, Jiang, Lei, Cai, Zheng, Sun, Wei, Hu, Hongkang, Lu, Chengyin, Jin, Weilin, Hu, Guohan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601647/
https://www.ncbi.nlm.nih.gov/pubmed/28938551
http://dx.doi.org/10.18632/oncotarget.16447
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author Zou, Yongxiang
Qiu, Guanzhong
Jiang, Lei
Cai, Zheng
Sun, Wei
Hu, Hongkang
Lu, Chengyin
Jin, Weilin
Hu, Guohan
author_facet Zou, Yongxiang
Qiu, Guanzhong
Jiang, Lei
Cai, Zheng
Sun, Wei
Hu, Hongkang
Lu, Chengyin
Jin, Weilin
Hu, Guohan
author_sort Zou, Yongxiang
collection PubMed
description 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.
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spelling pubmed-56016472017-09-21 Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin Zou, Yongxiang Qiu, Guanzhong Jiang, Lei Cai, Zheng Sun, Wei Hu, Hongkang Lu, Chengyin Jin, Weilin Hu, Guohan Oncotarget Research Paper 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. Impact Journals LLC 2017-03-22 /pmc/articles/PMC5601647/ /pubmed/28938551 http://dx.doi.org/10.18632/oncotarget.16447 Text en Copyright: © 2017 Zou et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zou, Yongxiang
Qiu, Guanzhong
Jiang, Lei
Cai, Zheng
Sun, Wei
Hu, Hongkang
Lu, Chengyin
Jin, Weilin
Hu, Guohan
Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title_full Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title_fullStr Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title_full_unstemmed Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title_short Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
title_sort overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601647/
https://www.ncbi.nlm.nih.gov/pubmed/28938551
http://dx.doi.org/10.18632/oncotarget.16447
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