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

研究成果: Article同行評審

19 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)131-141
頁數11
期刊Journal of Leukocyte Biology
99
發行號1
DOIs
出版狀態Published - 2016 1月

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 免疫學
  • 細胞生物學

指紋

深入研究「IL-18-induced interaction between IMP3 and HuR contributes to COX-2 mRNA stabilization in acute myeloid leukemia」主題。共同形成了獨特的指紋。

引用此