Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma.
Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma.
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DOI：
10.1038/bcj.2012.29
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发表时间：
2012-08-31
影响因子：
12.8
通讯作者：
Leoncini, L.
中科院分区：
文献类型：
--
作者：
Onnis, A.;Navari, M.;Antonicelli, G.;Morettini, F.;Mannucci, S.;De Falco, G.;Vigorito, E.;Leoncini, L.
EB病毒（EBV）是一种γ-疱疹病毒，感染>90%的人群。虽然EBV在健康携带者中以潜伏形式存在，但该病毒也与几种人类癌症有关。EB病毒与伯基特淋巴瘤（BL）密切相关，尽管EB病毒如何参与BL发病机制仍没有令人满意的解释。然而，最近已经提出了对病毒和microRNA（miRNAs）之间相互作用的新见解。特别地，已经显示EBV阳性BL中的B细胞分化在转录后水平上通过改变hsa-miR-127的表达而受损。在这里，我们表明hsa-miR-127的过表达是由于EBV编码的核抗原1（EBNA 1）的存在，并提供了这种病毒产物直接调节人miRNA的新机制的证据。最后，我们表明EBNA 1和hsa-miR-127的组合表达影响了人类记忆B细胞中主B细胞调节因子的表达，证实了先前在EBV阳性BL原发性肿瘤和细胞系中观察到的情况。对这些机制的深入了解将有助于阐明宿主和病原体之间复杂的调控网络，并有利于设计更特异性的EBV相关恶性肿瘤治疗方法。
Epstein-Barr Virus (EBV) is a γ-herpesvirus that infects >90% of the human population. Although EBV persists in its latent form in healthy carriers, the virus is also associated with several human cancers. EBV is strongly associated with Burkitt lymphoma (BL), even though there is still no satisfactory explanation of how EBV participates in BL pathogenesis. However, new insights into the interplay between viruses and microRNAs (miRNAs) have recently been proposed. In particular, it has been shown that B-cell differentiation in EBV-positive BL is impaired at the post-transcriptional level by altered expression of hsa-miR-127. Here, we show that the overexpression of hsa-miR-127 is due to the presence of the EBV-encoded nuclear antigen 1 (EBNA1) and give evidence of a novel mechanism of direct regulation of the human miRNA by this viral product. Finally, we show that the combinatorial expression of EBNA1 and hsa-miR-127 affects the expression of master B-cell regulators in human memory B cells, confirming the scenario previously observed in EBV-positive BL primary tumors and cell lines. A good understanding of these mechanisms will help to clarify the complex regulatory networks between host and pathogen, and favor the design of more specific treatments for EBV-associated malignancies.
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影响因子：
11.4
作者：
通讯作者：
--
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
5.4
作者：
Cameron, Jennifer E.;Yin, Qinyan;Flemington, Erik K.
通讯作者：
Flemington, Erik K.
影响因子：
6.4
作者：
Leucci, Eleonora;Onnis, Anna;Leoncini, Lorenzo
通讯作者：
Leoncini, Lorenzo
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude