B-cell differentiation in EBV-positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA-altered expression
B-cell differentiation in EBV-positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA-altered expression
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DOI：
10.1002/ijc.24655
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发表时间：
2010-03-15
影响因子：
6.4
通讯作者：
Leoncini, Lorenzo
中科院分区：
文献类型：
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作者：
Leucci, Eleonora;Onnis, Anna;Leoncini, Lorenzo
地方性、散发性和hiv相关的伯基特淋巴瘤（BL）都具有b细胞表型和MYC易位，但与eb病毒（EBV）的相关性不同。然而，EBV如何参与BL的发病机制仍没有令人满意的解释。最近的一项研究表明，EBV阳性和EBV阴性的BL有不同的起源细胞。特别是，根据免疫球蛋白基因突变分析，ebv阴性的BLs可能起源于早期的成中心细胞，而ebv阳性的BLs似乎起源于生发后的中心B细胞或记忆B细胞。因此，ebv阳性细胞中生发中心表型的出现可能源于b细胞分化受阻。从生发中心的退出涉及一系列复杂的事件，这些事件需要激活BLIMP-1，并随之下调几个目标基因。在这里，我们研究了预测参与b细胞分化的特异性mirna的表达，发现hsa-miR-127在ebv阳性和ebv阴性的BLs中表达差异。特别地，它只在ebv阳性的BL样本中被强烈上调，而ebv阴性病例的表达水平与正常对照相似，包括微解剖生发中心（GC）细胞。此外，我们发现hsa-miR-127通过转录后调控BLIMP1和XBP1参与b细胞分化过程的证据。因此，通过阻断b细胞分化过程，该miRNA的过表达可能代表了EBV阳性BL淋巴瘤形成的关键事件。
Endemic, sporadic and HIV-associated Burkitt lymphoma (BL) all have a B-cell phenotype and a MYC translocation, but a variable association with the Epstein-Barr virus (EBV). However, there is still no satisfactory explanation of how EBV participates in the pathogenesis of BL. A recent investigation suggested that EBV-positive and EBV-negative BL have different cells of origin. In particular, according to immunoglobulin gene mutation analysis, EBV-negative BLs may originate from early centroblasts, whereas EBV-positive BLs seem to arise from postgerminal center B cells or memory B cells. The appearance of a germinal center phenotype in EBV-positive cells might thus derive from a block in B-cell differentiation. The exit from the, germinal center involves a complex series of events, which require the activation of BLIMP-1, and the consequent downregulation of several target genes. Here, we investigated the expression of specific miRNAs predicted to be involved in B-cell differentiation and found that hsa-miR-127 is differentially expressed between EBV-positive and EBV-negative BLs. In particular, it was strongly upregulated only in EBV-positive BL samples, whereas EBV-negative cases showed levels of expression similar to normal controls, including microdissected germinal centers (GC) cells. In addition, we found evidence that hsa-miR-127 is involved in B-cell differentiation process through posttranscriptional regulation of BLIMP1 and XBP1. The overexpression of this miRNA may thus represent a key event in the lymphomagenesis of EBV positive BL, by blocking the B-cell differentiation process.