Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells
| Autor: | Liyuan Sun, Chunling Li, Shiyu Hao, Yancun Yin, Naili Zhang, Minjing Li, Huimin Xiao, Dongmei Zhao, Zhenhai Yu, Yanlian Xiong |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male MAP Kinase Kinase 4 THP-1 Cells lcsh:QR1-502 Apoptosis Biochemistry lcsh:Microbiology chemistry.chemical_compound Mice 0302 clinical medicine hemic and lymphatic diseases IL-2 receptor Phosphorylation RNA Small Interfering Anisomycin Aged 80 and over Gene knockdown Myeloid leukemia U937 Cells Middle Aged Prognosis Up-Regulation Gene Expression Regulation Neoplastic Leukemia Leukemia Myeloid Acute 030220 oncology & carcinogenesis Gene Knockdown Techniques bcl-Associated Death Protein SH3BP5 Growth inhibition Cell Survival Article 03 medical and health sciences Young Adult Cell Line Tumor medicine Animals Humans Viability assay Molecular Biology Adaptor Proteins Signal Transducing Aged Cell Proliferation Acute myeloid leukemia business.industry medicine.disease Survival Analysis 030104 developmental biology chemistry Cell culture Cancer research JNK business Neoplasm Transplantation |
| Zdroj: | Biomolecules Biomolecules, Vol 9, Iss 9, p 505 (2019) Volume 9 Issue 9 |
| ISSN: | 2218-273X |
| 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: | OpenAIRE |
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