Journal
BLOOD
Volume 119, Issue 9, Pages 2110-2113Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-11-394874
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Funding
- Internal Grant Agency of Ministry of Health Czech Republic (IGA MZCR) [NT11218-6/2010, CZ.1.05/1.1.00/02.0068, IGA MZCR NS10439-3/2009]
- Ministry of Education, Youth and Sports (MSMT) [MSM0021622430]
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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. (Blood. 2012; 119(9): 2110-2113)
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