Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77

2017 ◽  
Vol 65 (35) ◽  
pp. 7687-7697 ◽  
Author(s):  
Chengqiang Wang ◽  
Hui He ◽  
Guojun Dou ◽  
Juan Li ◽  
Xiaomei Zhang ◽  
...  
PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e28706 ◽  
Author(s):  
Sang-Hun Kang ◽  
Soo-Jin Jeong ◽  
Sun-Hee Kim ◽  
Ji-Hyun Kim ◽  
Ji Hoon Jung ◽  
...  

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 505
Author(s):  
Minjing Li ◽  
Shiyu Hao ◽  
Chunling Li ◽  
Huimin Xiao ◽  
Liyuan Sun ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xu Chen ◽  
Yuanyuan Qin ◽  
Zhenzhen Zhang ◽  
Zhengcao Xing ◽  
Qiqi Wang ◽  
...  

Leukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family that plays a crucial role in physiological and pathological processes. However, the role of ERG and its modification in leukemia remains underexplored. In the present study, we stably knocked down or overexpressed ERG in leukemia cells and observed that ERG significantly promotes the proliferation and inhibits the differentiation of AML (acute myeloid leukemia) cells. Further experiments showed that ERG was primarily modified by SUMO2, which was deconjugated by SENP2. PML promotes the SUMOylation of ERG, enhancing its stability. Arsenic trioxide decreased the expression level of ERG, further promoting cell differentiation. Furthermore, the mutation of SUMO sites in ERG inhibited its ability to promote the proliferation and inhibit the differentiation of leukemia cells. Our results demonstrated the crucial role of ERG SUMOylation in the development of AML, providing powerful targeted therapeutic strategies for the clinical treatment of AML.


2014 ◽  
Vol 1 (4) ◽  
pp. e970066 ◽  
Author(s):  
Evelyne Ségal-Bendirdjian ◽  
Mario P Tschan ◽  
Josy Reiffers ◽  
Mojgan Djavaheri-Mergny

2012 ◽  
Vol 53 ◽  
pp. S117-S118
Author(s):  
S. Misra⁎ ◽  
M. Wallenberg ◽  
A. Barsham ◽  
M. Björnstedt ◽  
A. Fernandes

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