Accumulation of miR-155 and BIC RNA in human B cell lymphomas
Accumulation of miR-155 and BIC RNA in human B cell lymphomas
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DOI：
10.1073/pnas.0500613102
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发表时间：
2005-03-08
影响因子：
11.1
通讯作者：
Dahlberg, JE
中科院分区：
文献类型：
--
作者：
Eis, PS;Tam, W;Dahlberg, JE
我们证明了microRNA miR-155可以从BIC RNA中存在的序列中加工而来，BIC RNA是一种剪接和多腺化但非蛋白质编码的RNA，积累在淋巴瘤细胞中。MiR-155的前体可能是瞬时剪接或非剪接的核BIC转录本，而不是积累的BIC RNA，后者主要是细胞质的。通过灵敏和定量的检测，我们发现包括弥漫性大B细胞淋巴瘤(DLBCL)在内的几种类型的B细胞淋巴瘤的临床分离株的miR-155拷贝数是正常循环B细胞的10-30倍。同样，淋巴瘤细胞中BIC RNA的数量也增加，但两种RNA量的比例并不是恒定的，这表明miR-155的水平受转录和加工的控制。B细胞表型活化的DLBCL中miR-155的表达水平明显高于生发中心表型。由于活化的B细胞型DLBCL患者的临床预后较差，因此定量检测这种微小RNA可能有助于诊断。
We show that the microRNA miR-155 can be processed from sequences present in BIC RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in lymphoma cells. The precursor of miR-155 is likely a transient spliced or unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is primarily cytoplasmic. By using a sensitive and quantitative assay, we find that clinical isolates of several types of B cell lymphomas, including diffuse large B cell lymphoma (DLBCL), have 10-to 30-fold higher copy numbers of miR-155 than do normal circulating B cells. Similarly, the quantities of BIC RNA are elevated in lymphoma cells, but ratios of the amounts of the two RNAs are not constant, suggesting that the level of miR-155 is controlled by transcription and processing. Significantly higher levels of miR-155 are present in DLBCLs with an activated B cell phenotype than with the germinal center phenotype. Because patients with activated B cell-type DLBCL have a poorer clinical prognosis, quantification of this microRNA may be diagnostically useful.