MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia
Authors | |
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Year of publication | 2012 |
Type | Article in Periodical |
Magazine / Source | Blood |
MU Faculty or unit | |
Citation | |
Web | http://bloodjournal.hematologylibrary.org/content/119/9/2110 |
Doi | http://dx.doi.org/10.1182/blood-2011-11-394874 |
Field | Oncology and hematology |
Keywords | CLL PATIENTS; SURVIVAL; SUBTYPES |
Description | 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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