PUBLICATION
EVI-1 Modulates Arsenic Trioxide induced Apoptosis through JNK signaling pathway in Leukemia Cells
- Authors
- Lang, W., Zhu, J., Chen, F., Cai, J., Zhong, J.
- ID
- ZDB-PUB-181127-69
- Date
- 2018
- Source
- Experimental cell research 374(1): 140-151 (Journal)
- Registered Authors
- Chen, Fangyuan, Zhong, Ji-Hua
- Keywords
- EVI-1, acute leukemia, apoptosis, arsenic trioxide, c-Jun N-terminal kinase
- MeSH Terms
-
- Animals
- Anthracenes/pharmacology
- Apoptosis/drug effects*
- Arsenic Trioxide/pharmacology*
- Cell Line, Tumor
- Disease Models, Animal
- Down-Regulation/drug effects
- Gene Expression Regulation, Leukemic/drug effects
- Humans
- Leukemia/genetics
- Leukemia/metabolism*
- Leukemia/pathology*
- MAP Kinase Signaling System/drug effects*
- MDS1 and EVI1 Complex Locus Protein/metabolism*
- Models, Biological
- Neoplasm Proteins/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Zebrafish
- PubMed
- 30472098 Full text @ Exp. Cell Res.
Citation
Lang, W., Zhu, J., Chen, F., Cai, J., Zhong, J. (2018) EVI-1 Modulates Arsenic Trioxide induced Apoptosis through JNK signaling pathway in Leukemia Cells. Experimental cell research. 374(1):140-151.
Abstract
High expression of the oncogene ecotropic viral integration site-1 (EVI-1) is an independent negative prognostic indicator of survival in leukemia patients. This study aimed to examine the effects of arsenic trioxide (ATO) on EVI-1 in acute myeloid leukemia (AML). Mononuclear cells were isolated from the bone marrow and peripheral blood of AML patients and healthy donors. EVI-1 expression in hematopoietic cells was evaluated by RT-qPCR and Western blot analysis. EVI-1 was highly expressed in both primary AML and leukemia cell lines (THP-1 and K562). ATO down-regulated EVI-1 mRNA in zebrafish in vivo as well as in primary leukemia cells and THP-1 and K562 cells in vitro. Additionally, ATO treatment induced apoptosis, down-regulated both EVI-1 mRNA and oncoprotein expression, increased the expression of pro-apoptosis proteins, and decreased the expression of anti-apoptotic proteins in leukemia cells in vitro. EVI-1 expression in leukemia cells (THP-1 and K562) transduced with EVI-1 siRNA was significantly reduced. Silencing EVI-1 had a significant effect on the activation of the JNK pathway and the induction of leukemia cell apoptosis. ATO may downregulate EVI-1 mRNA and oncoprotein levels and block the inhibitory effects of EVI-1 on the JNK pathway, which activates the JNK apoptotic pathway, thereby leading to the apoptosis of EVI-1 in AML patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping