MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia
MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia
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DOI：
10.1182/blood-2011-11-394874
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发表时间：
2012-03-01
期刊：
影响因子：
20.3
通讯作者：
Pospisilova, Sarka
中科院分区：
文献类型：
--
作者：
Mraz, Marek;Dolezalova, Dasa;Pospisilova, Sarka
MicroRNA (miRNA) 在慢性淋巴细胞白血病以及正常 B 细胞中发挥着关键作用。值得注意的是，编码 miR-650 及其同源物的 miRNA 基因与编码 lambda 免疫球蛋白 (IgL lambda) 的几个可变 (V) 子基因重叠。最近的研究描述了 miR-650 在实体瘤中的作用，但其在慢性淋巴细胞白血病 (CLL) 中的作用尚未研究。我们的实验表明，miR-650 的表达是通过与其 IgL lambda 宿主基因的偶联表达来调节的。这种耦合为 microRNA 基因调控提供了一种独特但未被观察到的机制。我们确定 miR-650 的较高表达与良好的 CLL 预后相关，并影响 B 细胞的增殖能力。我们还确定，在 B 细胞中，miR-650 靶向对细胞增殖和存活至关重要的蛋白质：细胞周期蛋白依赖性激酶 1 (CDK1)、生长抑制剂 4 (ING4) 和早期 B 细胞因子 3 (EBF3)。这项研究强调了 miR-650 在 CLL 生物学和正常 B 细胞生理学中的重要性。 （血。2012；119（9）：2110-2113）
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)