Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells

Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that...

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Autores principales: Li, Minjing, Hao, Shiyu, Li, Chunling, Xiao, Huimin, Sun, Liyuan, Yu, Zhenhai, Zhang, Naili, Xiong, Yanlian, Zhao, Dongmei, Yin, Yancun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770748/
https://www.ncbi.nlm.nih.gov/pubmed/31546831
http://dx.doi.org/10.3390/biom9090505
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author Li, Minjing
Hao, Shiyu
Li, Chunling
Xiao, Huimin
Sun, Liyuan
Yu, Zhenhai
Zhang, Naili
Xiong, Yanlian
Zhao, Dongmei
Yin, Yancun
author_facet Li, Minjing
Hao, Shiyu
Li, Chunling
Xiao, Huimin
Sun, Liyuan
Yu, Zhenhai
Zhang, Naili
Xiong, Yanlian
Zhao, Dongmei
Yin, Yancun
author_sort Li, Minjing
collection PubMed
description Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that the elevated expression of SH3 domain-binding protein 5 (SH3BP5) significantly correlates with poor outcomes of AML patients. To test whether SH3BP5 contributes to the growth and survival of AML cells, we use the shRNA-encoding lentivirus system to achieve the knockdown of SH3BP5 expression in human AML cell lines U937, THP-1, Kasumi-1, and MV4-11. Functionally, the knockdown of SH3BP5 expression markedly inhibits the cell viability and induced apoptosis of these leukemia cells. Mechanistically, western blot analysis indicates that the knockdown of SH3BP5 expression decreases the phosphorylation of JNK and BAD. Moreover, the JNK agonist anisomycin rescues the growth inhibition phenotype of SH3BP5 deficiency in THP-1 cells. Moreover, the expression of SH3BP5 positively correlates with CD25 and CD123 levels. Finally, our study highlights the crucial role of SH3BP5 in promoting the survival of AML cells, and its suppression may be a potential therapeutic strategy for treating human AML.
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spelling pubmed-67707482019-10-30 Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells Li, Minjing Hao, Shiyu Li, Chunling Xiao, Huimin Sun, Liyuan Yu, Zhenhai Zhang, Naili Xiong, Yanlian Zhao, Dongmei Yin, Yancun Biomolecules Article Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that the elevated expression of SH3 domain-binding protein 5 (SH3BP5) significantly correlates with poor outcomes of AML patients. To test whether SH3BP5 contributes to the growth and survival of AML cells, we use the shRNA-encoding lentivirus system to achieve the knockdown of SH3BP5 expression in human AML cell lines U937, THP-1, Kasumi-1, and MV4-11. Functionally, the knockdown of SH3BP5 expression markedly inhibits the cell viability and induced apoptosis of these leukemia cells. Mechanistically, western blot analysis indicates that the knockdown of SH3BP5 expression decreases the phosphorylation of JNK and BAD. Moreover, the JNK agonist anisomycin rescues the growth inhibition phenotype of SH3BP5 deficiency in THP-1 cells. Moreover, the expression of SH3BP5 positively correlates with CD25 and CD123 levels. Finally, our study highlights the crucial role of SH3BP5 in promoting the survival of AML cells, and its suppression may be a potential therapeutic strategy for treating human AML. MDPI 2019-09-19 /pmc/articles/PMC6770748/ /pubmed/31546831 http://dx.doi.org/10.3390/biom9090505 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Minjing
Hao, Shiyu
Li, Chunling
Xiao, Huimin
Sun, Liyuan
Yu, Zhenhai
Zhang, Naili
Xiong, Yanlian
Zhao, Dongmei
Yin, Yancun
Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title_full Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title_fullStr Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title_full_unstemmed Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title_short Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
title_sort elevated sh3bp5 correlates with poor outcome and contributes to the growth of acute myeloid leukemia cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770748/
https://www.ncbi.nlm.nih.gov/pubmed/31546831
http://dx.doi.org/10.3390/biom9090505
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