IL-18-induced interaction between IMP3 and HuR contributes to COX-2 mRNA stabilization in acute myeloid leukemia

Chiung Yuan Ko, Wen Ling Wang, Chien Feng Li, Yung Ming Jeng, Yu Yi Chu, Han Ying Wang, Ta-Chien Tseng, Ju-Ming Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 insulinlike 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 mRNAbinding protein 3 from the nucleus to the cytoplasm and facilitated their interaction; subsequently, this complex bound to the 39 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.

Original languageEnglish
Pages (from-to)131-141
Number of pages11
JournalJournal of Leukocyte Biology
Volume99
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

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Interleukin-18
Cyclooxygenase 2
Acute Myeloid Leukemia
Messenger RNA
Drug Resistance
Antigens
Interleukin-18 Receptors
Untranslated Regions
U937 Cells
RNA-Binding Proteins
Somatomedins
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Cytoplasm
Leukemia
Therapeutics
Cytokines
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Ko, Chiung Yuan ; Wang, Wen Ling ; Li, Chien Feng ; Jeng, Yung Ming ; Chu, Yu Yi ; Wang, Han Ying ; Tseng, Ta-Chien ; Wang, Ju-Ming. / IL-18-induced interaction between IMP3 and HuR contributes to COX-2 mRNA stabilization in acute myeloid leukemia. In: Journal of Leukocyte Biology. 2016 ; Vol. 99, No. 1. pp. 131-141.
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IL-18-induced interaction between IMP3 and HuR contributes to COX-2 mRNA stabilization in acute myeloid leukemia. / Ko, Chiung Yuan; Wang, Wen Ling; Li, Chien Feng; Jeng, Yung Ming; Chu, Yu Yi; Wang, Han Ying; Tseng, Ta-Chien; Wang, Ju-Ming.

In: Journal of Leukocyte Biology, Vol. 99, No. 1, 01.01.2016, p. 131-141.

Research output: Contribution to journalArticle

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