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MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia

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MRÁZ Marek DOLEŽALOVÁ Dáša PLEVOVÁ Karla STAŇO KOZUBÍK Kateřina MAYEROVÁ Veronika ČERNÁ Kateřina MUSILOVÁ Kateřina TICHÝ Boris PAVLOVÁ Šárka BORSKÝ Marek VERNER Jan DOUBEK Michael BRYCHTOVÁ Yvona TRBUŠEK Martin HAMPL Aleš MAYER Jiří POSPÍŠILOVÁ Šárka

Rok publikování 2012
Druh Článek v odborném periodiku
Časopis / Zdroj Blood
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://bloodjournal.hematologylibrary.org/content/119/9/2110
Doi http://dx.doi.org/10.1182/blood-2011-11-394874
Obor Onkologie a hematologie
Klíčová slova CLL PATIENTS; SURVIVAL; SUBTYPES
Popis MicroRNAs (miRNAs) play a key role in chronic lymphocytic leukemia as well as in normal B cells. Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgL lambda). Recent studies describe the role of miR-650 in solid tumors, but its role in chronic lymphocytic leukemia (CLL) has not yet been studied. Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgL lambda. This coupling provides a unique yet unobserved mechanism for microRNA gene regulation. We determine that higher expression of miR-650 is associated with a favorable CLL prognosis and influences the proliferation capacity of B cells. We also establish that in B cells, miR-650 targets proteins important in cell proliferation and survival: cyclin dependent kinase 1 (CDK1), inhibitor of growth 4 (ING4), and early B-cell factor 3 (EBF3). This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology.
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