Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma
Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma
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DOI：
10.1038/sj.onc.1210147
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发表时间：
2007-05-31
期刊：
影响因子：
8
通讯作者：
Kroesen, B-J
中科院分区：
文献类型：
--
作者：
Kluiver, J.;van den Berg, A.;Kroesen, B-J
BIC是一种初级microRNA（pri-miR-155），可以加工成成熟的miR-155。在这项研究中，我们发现蛋白激酶C（PKC）和核因子-κ B（NF-κ B）在B细胞受体触发后BIC表达的调节中起着至关重要的作用。令人惊讶的是，在伯基特淋巴瘤衍生的拉莫斯细胞系中诱导BIC表达后，北方印迹分析没有揭示任何miR-155表达，而其他微RNA是明显可检测的。BIC在拉莫斯和HEK 293细胞中的异位表达导致miR-155在HEK 293中表达，但在拉莫斯细胞中不表达，表明BIC对拉莫斯中miR-155加工的特异性阻断。与使用拉莫斯获得的结果一致，在其他伯基特淋巴瘤细胞系中也观察到诱导BIC表达后缺乏miR-155表达，表明伯基特淋巴瘤中BIC加工中的通用和特异性阻断。相反，在正常扁桃体B细胞中诱导BIC表达导致非常高水平的miR-155表达和在霍奇金淋巴瘤细胞系中诱导BIC表达。它还导致miR-155水平升高。我们的数据为成熟miR-155表达的两个水平的调节提供了证据：一个在涉及PKC和NF-κ B的转录水平，一个在加工水平。伯基特淋巴瘤细胞不仅表达低水平的BIC，而且通过一种迄今未知的机制阻止BIC的加工。
BIC is a primary microRNA (pri-miR-155) that can be processed to mature miR-155. In this study, we show the crucial involvement of protein kinase C (PKC) and nuclear factor-kappa B (NF-kappa B) in the regulation of BIC expression upon B-cell receptor triggering. Surprisingly, Northern blot analysis did not reveal any miR-155 expression upon induction of BIC expression in the Burkitt lymphoma-derived Ramos cell line, whereas other microRNAs were clearly detectable. Ectopic expression of BIC in Ramos and HEK293 cells resulted in miR-155 expression in HEK293, but not in Ramos cells, suggesting a specific block of BIC to miR-155 processing in Ramos. In line with the results obtained with Ramos, lack of miR-155 expression after induction of BIC expression was also observed in other Burkitt lymphoma cell lines, indicating a generic and specific blockade in the processing of BIC in Burkitt lymphoma. In contrast, induction of BIC expression in normal tonsillar B cells resulted in very high levels of miR-155 expression and induction of BIC expression in Hodgkin's lymphoma cell lines. It also resulted in elevated levels of miR-155. Our data provide evidence for two levels of regulation for mature miR-155 expression: one at the transcriptional level involving PKC and NF-kappa B, and one at the processing level. Burkitt lymphoma cells not only express low levels of BIC, but also prevent processing of BIC via an, as yet, unknown mechanism.