Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia
| Autor: | Oleh Petriv, Jens Ruschmann, Edith Schneider, Lars Palmqvist, Kathrin Krowiorz, Anna Staffas, Erik Delsing Malmberg, Carl L. Hansen, Hartmut Döhner, Arefeh Rouhi, Florian Kuchenbauer, Martin Hirst, Arghavan Ashouri, Ping Xiang, Michael Heuser, Konstanze Döhner, Stella Yuan Wei, Lars Bullinger, Christina Miller, Linda Röhner, Nicole Pochert, R. Keith Humphries, Laleh S. Arabanian, Alireza Heravi-Moussavi, Christian Buske, Linda Fogelstrand |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Acute Myeloid Leukemia Carcinogenesis Article Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine In vivo hemic and lymphatic diseases microRNA Medicine Animals Humans Myeloid Ecotropic Viral Integration Site 1 Protein Homeodomain Proteins Oncogene business.industry Gene Expression Regulation Leukemic Myeloid leukemia Hematology medicine.disease Pathophysiology Leukemia Leukemia Myeloid Acute MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research business Homing (hematopoietic) |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo. However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia. |
| Databáze: | OpenAIRE |
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