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IL-18-induced interaction between IMP3 and HuR contributes to COX-2 mRNA stabilization in acute myeloid leukemia
- Source :
- Journal of Leukocyte Biology. 99:131-141
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Acute myeloid leukemia is the majority type presented in leukemia patients. Forcing malignant cells to undergo differentiation is 1 strategy for acute myeloid leukemia therapy. However, the failure of acute myeloid leukemia patients to achieve remission as a result of drug resistance remains a challenge. In this study, we found that the abundances of the proinflammatory cytokine IL-18 and its receptor (IL-18R) correlated with the occurrence of drug resistance in AML patients during standard treatment. Cyclooxygenase 2 (COX-2) has been suggested to have an antiapoptotic role in chemoresistant cancer cells. IL-18 treatment resulted in an increase in COX-2 expression through the post-transcriptional regulation of COX-2 mRNA in differentiated U937 cells and showed antiapoptotic activity in U937 and THP-1 cells. Two RNA-binding proteins, human antigen R and insulin-like growth factor mRNA-binding protein 3, mediated the stabilization of COX-2 mRNA. IL-18 induced the shuttling of human antigen R and insulin-like growth factor mRNA-binding protein 3 from the nucleus to the cytoplasm and facilitated their interaction; subsequently, this complex bound to the 3′ untranslated region of COX-2 mRNA and affected its stability. We demonstrated further that JNK and/or ERK1/2 regulated human antigen R nucleocytoplasmic shuttling, mediating IL-18 stabilization of cyclooxygenase 2 mRNA.
- Subjects :
- Transcriptional Activation
0301 basic medicine
Untranslated region
MAP Kinase Signaling System
RNA Stability
Immunology
Biology
ELAV-Like Protein 1
03 medical and health sciences
Differentiation therapy
Cell Line, Tumor
medicine
Humans
Immunology and Allergy
CD135
RNA, Messenger
RNA Processing, Post-Transcriptional
Interleukin-18
RNA-Binding Proteins
Myeloid leukemia
Cell Biology
MRNA stabilization
medicine.disease
Molecular biology
Leukemia, Myeloid, Acute
Leukemia
030104 developmental biology
Cyclooxygenase 2
Cancer cell
Interleukin 18
Protein Binding
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....fcf46c1f4790f4d1c368ba69b6bc0d50