Institute of Integrated Medicine, Binzhou Medical University, Yantai 264003, China.
School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, China.
Biomolecules. 2019 Sep 19;9(9):505. doi: 10.3390/biom9090505.
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.
目前的治疗策略在治疗急性髓细胞白血病 (AML) 方面并不特别成功。鉴定和描述对白血病细胞的存活和生长至关重要的癌基因将为开发新疗法提供潜在的靶点。在这里，我们报告 SH3 结构域结合蛋白 5 (SH3BP5) 的表达升高与 AML 患者的不良预后显著相关。为了测试 SH3BP5 是否有助于 AML 细胞的生长和存活，我们使用 shRNA 编码的慢病毒系统在人 AML 细胞系 U937、THP-1、Kasumi-1 和 MV4-11 中实现 SH3BP5 表达的敲低。功能上，SH3BP5 表达的敲低显著抑制这些白血病细胞的细胞活力并诱导细胞凋亡。机制上，Western blot 分析表明，SH3BP5 表达的敲低降低了 JNK 和 BAD 的磷酸化。此外，JNK 激动剂 anisomycin 挽救了 SH3BP5 缺陷对 THP-1 细胞生长抑制表型的影响。此外，SH3BP5 的表达与 CD25 和 CD123 水平呈正相关。最后，我们的研究强调了 SH3BP5 在促进 AML 细胞存活中的关键作用，其抑制可能是治疗人类 AML 的一种潜在治疗策略。
