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MicroRNA-708 is a n...
MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.
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Schneider, Edith (author)
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Pochert, Nicole (author)
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Ruess, Christoph (author)
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MacPhee, Liam (author)
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Escano, Leo (author)
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Miller, Christina (author)
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Krowiorz, Kathrin (author)
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- Delsing Malmberg, Erik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Heravi-Moussavi, Alireza (author)
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Lorzadeh, Alireza (author)
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- Ashouri, Arghavan, 1987 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Grasedieck, Sarah (author)
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Sperb, Nadine (author)
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- Kopparapu, Pradeep Kumar (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för biomedicin,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Biomedicine
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Iben, Sebastian (author)
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- Staffas, Anna, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Xiang, Ping (author)
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Rösler, Reinhild (author)
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- Kanduri, Meena, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Larsson, Erik (author)
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- Fogelstrand, Linda, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Döhner, Hartmut (author)
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Döhner, Konstanze (author)
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Wiese, Sebastian (author)
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Hirst, Martin (author)
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Keith Humphries, R (author)
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- Palmqvist, Lars, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Kuchenbauer, Florian (author)
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Rouhi, Arefeh (author)
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(creator_code:org_t)
- 2019-11-25
- 2020
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 34, s. 1253-1265
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Abstract
Subject headings
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- MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
- art (subject category)
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Leukemia
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To the university's database
- By the author/editor
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Schneider, Edith
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Pochert, Nicole
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Ruess, Christoph
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MacPhee, Liam
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Escano, Leo
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Miller, Christin ...
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show more...
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Krowiorz, Kathri ...
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Delsing Malmberg ...
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Heravi-Moussavi, ...
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Lorzadeh, Alirez ...
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Ashouri, Arghava ...
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Grasedieck, Sara ...
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Sperb, Nadine
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Kopparapu, Prade ...
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Iben, Sebastian
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Staffas, Anna, 1 ...
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Xiang, Ping
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Rösler, Reinhild
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Kanduri, Meena, ...
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Larsson, Erik
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Fogelstrand, Lin ...
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Döhner, Hartmut
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Döhner, Konstanz ...
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Wiese, Sebastian
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Hirst, Martin
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Keith Humphries, ...
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Palmqvist, Lars, ...
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Kuchenbauer, Flo ...
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Rouhi, Arefeh
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Leukemia
- By the university
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University of Gothenburg