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

Autor: Minjing Li, Shiyu Hao, Chunling Li, Huimin Xiao, Liyuan Sun, Zhenhai Yu, Naili Zhang, Yanlian Xiong, Dongmei Zhao, Yancun Yin
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Biomolecules, Vol 9, Iss 9, p 505 (2019)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom9090505
Popis: 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.
Databáze: Directory of Open Access Journals
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