Ko C.-Y.Wang W.-L.Li C.-F.YUNG-MING JENGChu Y.-Y.Wang H.-Y.Tseng J.T.Wang J.-M.2020-03-062020-03-0620160741-5400https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953439694&doi=10.1189%2fjlb.2A0414-228RR&partnerID=40&md5=1f2666f72b0f85c06ab6e5eb4ca227e9https://scholars.lib.ntu.edu.tw/handle/123456789/473300Acute 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. ? Society for Leukocyte Biology.[SDGs]SDG3antigen; binding protein; cyclooxygenase 2; human antigen r; insulin like growth factor 11 mRNA binding protein 3; interleukin 18 receptor; lentivirus vector; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; RNA binding protein; unclassified drug; cyclooxygenase 2; ELAV like protein 1; IMP3 protein, human; interleukin 18; messenger RNA; protein binding; RNA binding protein; 3' untranslated region; acute myeloblastic leukemia; Article; bone marrow biopsy; cell count; cell death; cell differentiation; cell proliferation; cell survival; clinical article; cytosolic fraction; gene silencing; human; human cell; immunohistochemistry; priority journal; protein expression; protein interaction; reverse transcription polymerase chain reaction; RNA processing; signal transduction; acute myeloblastic leukemia; drug effects; genetics; metabolism; RNA stability; transcription initiation; tumor cell line; Cell Line, Tumor; Cyclooxygenase 2; ELAV-Like Protein 1; Humans; Interleukin-18; Leukemia, Myeloid, Acute; MAP Kinase Signaling System; Protein Binding; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger; RNA-Binding Proteins; Transcriptional Activationjournal article10.1189/jlb.2A0414-228RR263421052-s2.0-84953439694