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, Joseph T. Tseng, Ju Ming Wang

Research output: Contribution to journalArticle

7 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 - Jan 1 2016

Keywords

  • Differentiation therapy
  • Drug resistance
  • Post-transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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