Virally Induced Cellular MicroRNA miR-155 Plays a Key Role in B-Cell Immortalization by Epstein-Barr Virus
Virally Induced Cellular MicroRNA miR-155 Plays a Key Role in B-Cell Immortalization by Epstein-Barr Virus
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病毒诱导的细胞微RNA miR-155在爱泼斯坦-巴氏病毒导致的B细胞不死过程中发挥关键作用
DOI：
10.1128/jvi.01248-10
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发表时间：
2010-11-01
影响因子：
5.4
通讯作者：
Cullen, Bryan R.
中科院分区：
文献类型：
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作者：
Linnstaedt, Sarah D.;Gottwein, Eva;Cullen, Bryan R.
Epstein-Barr病毒（EBV）感染静息的原代人B细胞导致其转化为无限增殖的淋巴母细胞样细胞系（LCL）。LCL形成作为淋巴瘤发生的模型，并且LCL在表型上类似于EBV阳性弥漫性大B细胞淋巴瘤（DLBCL），其代表常见的AIDS相关恶性肿瘤。EB病毒感染B细胞可诱导多种细胞微小RNA（miRNA）的表达，最显著的是miR-155，其在许多肿瘤中过表达，并且当在动物中过表达时可诱导B细胞淋巴瘤。在这里，我们证明了miR-155是LCL中最高表达的miRNA，并且选择性抑制miR-155功能特异性抑制LCL和DLBCL细胞系IBL-1的生长。缺乏miR-155的细胞在S期进展中效率低下，并自发地经历凋亡。相比之下，其他三个B细胞淋巴瘤细胞系，包括两个EBV阳性伯基特淋巴瘤细胞系，在缺乏miR-155功能的情况下正常生长。这些数据确定EBV诱导细胞miR-155表达对于实验室产生的LCL和天然存在的DLBCL的生长都是至关重要的，并且表明靶向抑制miR-155功能可以代表体内治疗DLBCL的新方法。
Infection of resting primary human B cells by Epstein-Barr virus (EBV) results in their transformation into indefinitely proliferating lymphoblastoid cell lines (LCLs). LCL formation serves as a model for lymphomagenesis, and LCLs are phenotypically similar to EBV-positive diffuse large B-cell lymphomas (DLBCLs), which represent a common AIDS-associated malignancy. B-cell infection by EBV induces the expression of several cellular microRNAs (miRNAs), most notably miR-155, which is overexpressed in many tumors and can induce B-cell lymphomas when overexpressed in animals. Here, we demonstrate that miR-155 is the most highly expressed miRNA in LCLs and that the selective inhibition of miR-155 function specifically inhibits the growth of both LCLs and the DLBCL cell line IBL-1. Cells lacking miR-155 are inefficient in progressing through S phase and spontaneously undergo apoptosis. In contrast, three other B-cell lymphoma lines, including two EBV-positive Burkitt's lymphoma cell lines, grew normally in the absence of miR-155 function. These data identify the induction of cellular miR-155 expression by EBV as critical for the growth of both laboratory-generated LCLs and naturally occurring DLBCLs and suggest that targeted inhibition of miR-155 function could represent a novel approach to the treatment of DLBCL in vivo.