6533b82cfe1ef96bd128f558
RESEARCH PRODUCT
Quaking and miR-155 interactions in inflammation and leukemogenesis.
Dario VenezianoRi CuiCecilia FernandesTaewan KimStefano VoliniaLaura Z. RassentiThomas J. KippsCarlo M. CroceHamdy AwadTyler SheetzJean Jacques MichailleJean Jacques MichailleTim RichmondDario PalmieriMelissa BrownHui Lung SunMarcela ChiabaiEsmerina TiliAlessandro Laganàsubject
LipopolysaccharidesTime Factorsmedicine.medical_treatmentmedicine.disease_causeTransgenicMiceInnatePhosphorylationChronicB-LymphocytesLeukemiaRNA-Binding ProteinsU937 CellsLymphocyticCell biologyCytokineOncologyPhosphorylationCytokinesCLL; Glioblastoma; Inflammation; MiR-155; QKI; Animals; Apoptosis Regulatory Proteins; B-Lymphocytes; Case-Control Studies; Cytokines; Humans; Immunity Innate; Inflammation; Leukemia Lymphocytic Chronic B-Cell; Lipopolysaccharides; Macrophages; Mice; Mice Transgenic; MicroRNAs; Mitogen-Activated Protein Kinases; Phosphorylation; RAW 264.7 Cells; RNA-Binding Proteins; Signal Transduction; Time Factors; Transfection; U937 Cells; OncologySignal transductionMitogen-Activated Protein KinasesSignal Transductionp38 mitogen-activated protein kinasesOncology and CarcinogenesisMice TransgenicTransfectionNOmiR-155miR-155Downregulation and upregulationmicroRNAmedicineAnimalsHumansInflammationQKIbusiness.industryMacrophagesB-CellImmunityglioblastomaLeukemia Lymphocytic Chronic B-CellImmunity InnateMicroRNAsRAW 264.7 CellsCase-Control StudiesImmunologyCarcinogenesisbusinessApoptosis Regulatory ProteinsCLLPriority Research Paperdescription
Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1β and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eµ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved.
year | journal | country | edition | language |
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2015-09-01 |