Priority Research Papers:
Quaking and miR-155 interactions in inflammation and leukemogenesis
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Esmerina Tili1,2,*, Marcela Chiabai2,*, Dario Palmieri2,*, Melissa Brown2, Ri Cui2, Cecilia Fernandes2, Tim Richmond2, Taewan Kim3, Tyler Sheetz2, Hui-Lung Sun2, Alessandro Lagana4, Dario Veneziano2, Stefano Volinia5, Laura Rassenti6, Thomas Kipps6, Hamdy Awad1, Jean-Jacques Michaille2,7 and Carlo M. Croce2
1 Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
2 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Wexner Medical Center and Comprehensive Cancer Center, Columbus, OH, USA
3 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
5 University of Ferrara, Department of Morphology, Surgery and Experimental Medicine, Ferrara, Italy
6 CLL Research Consortium, Moores UCSD Cancer Center, La Jolla, CA, USA
7 BioPerox-IL, UB-INSERM IFR #100, Université de Bourgogne, Faculté Gabriel, Gabriel, Dijon, France
* These authors have contributed equally to this work
Esmerina Tili, email:
Carlo M. Croce, email:
Keywords: miR-155, CLL, inflammation, QKI, glioblastoma
Received: July 08, 2015 Accepted: August 18, 2015 Published: August 24, 2015
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.
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