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

Journal of Leukocyte Biology
Chiung-Yuan KoJu-Ming Wang

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 demonstrate...Continue Reading

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Citations

May 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dmitrii SemenokAthina Geronikaki
Feb 25, 2017·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Xiaohui XuJudong Luo
Sep 12, 2019·Journal of Receptor and Signal Transduction Research·Stephnie Kang-Xian YiauMaha Abdullah
Feb 6, 2020·Frontiers in Cell and Developmental Biology·Caterina Mancarella, Katia Scotlandi
Apr 14, 2020·Current Pharmaceutical Design·Peng-Fei WangShu-Lin Liu
Jul 13, 2021·Investigational New Drugs·Qiu-Ying DuDong-Sheng Pei

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