Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells
Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells
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Epstein-Barr 病毒通过癌蛋白潜膜蛋白 1 下调 MicroRNA 203：导致上皮细胞肿瘤发病率增加
DOI：
10.1128/jvi.05901-11
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Guiyuan Li
中科院分区：
文献类型：
--
作者：
Qianjin Liao;Zhaoyang Zeng;Junyi Zhang;Guiyuan Li
**摘要** 爱泼斯坦 - 巴尔病毒（EBV）与鼻咽癌（NPC）高度相关，它调控着一些参与癌症发生发展的微小核糖核酸（miRNA）。EBV在细胞miRNA失调中所起的作用以及这如何…… （原文此处“af”不完整，可能影响完整理解与翻译）
ABSTRACT The Epstein-Barr virus (EBV) is highly associated with nasopharyngeal carcinoma (NPC), and it regulates some microRNAs (miRNAs) that are involved in the development of cancer. The role of EBV in the deregulation of cellular miRNAs and how this affects the progression of NPC remain to be investigated. An analysis of the miRNA profile in an EBV-infected cell line revealed that miRNA 203 (miR-203) was downregulated. miR-203 is expressed specifically in epithelial cells. This downregulation of miR-203 was further verified and functionally analyzed. miR-203 was downregulated substantially in epithelial cells and NPC tissues that were latently infected with EBV. Downregulation of miR-203 also occurred during the early stage of EBV infection. Furthermore, the viral oncoprotein, latent membrane protein 1 (LMP1), was responsible for downregulation of miR-203. Removal of the latent EBV genome or suppression of LMP1 resulted in restoration of miR-203 expression. EBV-LMP1 mediated the downregulation of miR-203 at the primary transcript level. E2F3 and CCNG1 were identified as target genes of miR-203. Ectopic expression of miR-203 inhibited EBV-induced S-phase entry and transformation in vivo. Overexpression of the targets overcame the effects of miR-203 mimics on the cell cycle, and the expression of target genes in tumor models was inhibited by miR-203. Inhibitors of Jun N-terminal protein kinase (JNK) and NF-κB blocked miR-203 downregulation. These results imply that EBV promotes malignancy by downregulating cellular miR-203, which contributes to the etiology of NPC.
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影响因子：
64.8
作者：
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Golub, TR
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