NF-kappa B Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma
文献类型:期刊论文
作者 | Verhoeven RJA1; Tong S1; Jin DY4; Chen MR5; Pan JJ2; Chen HL1; Zhang GH1,6; Zong JF2; Chen YX[*]3 |
刊名 | JOURNAL OF VIROLOGY
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出版日期 | 2016 |
卷号 | 90期号:14页码:6475-6488 |
通讯作者 | hlchen@hku.hk |
合作状况 | 其它 |
英文摘要 | Epstein-Barr virus (EBV) expresses few viral proteins in nasopharyngeal carcinoma (NPC) but high levels of BamHI-A rightward transcripts (BARTs), which include long noncoding RNAs (lncRNAs) and BART microRNAs (miRNAs). It is hypothesized that the mechanism for regulation of BARTs may relate to EBV pathogenesis in NPC. Weshowed that nuclear factor-kappa B (NF-kappa B) activates the BART promoters and modulates the expression of BARTs in EBV-infected NPC cells but that introduction of mutations into the putative NF-kappa B binding sites abolished activation of BART promoters by NF-kappa B. Binding of p50 subunits to NF-kappa B sites in the BART promoters was confirmed in electrophoretic mobility shift assays (EMSA) and further demonstrated in vivo using chromatin immunoprecipitation (ChIP) analysis. Expression of BART miRNAs and lncRNAs correlated with NF-kappa B activity in EBV-infected epithelial cells, while treatment of EBV-harboring NPC C666-1 cells with aspirin (acetylsalicylic acid [ASA]) and the I kappa B kinase inhibitor PS-1145 inhibited NF-kappa B activity, resulting in downregulation of BART expression. Expression of EBV LMP1 activates BART promoters, whereas an LMP1 mutant which cannot induce NF-kappa B activation does not activate BART promoters, further supporting the idea that expression of BARTs is regulated by NF-kappa B signaling. Expression of LMP1 is tightly regulated in NPC cells, and this study confirmed that miR-BART5-5p downregulates LMP1 expression, suggesting a feedback loop between BART miRNA and LMP1-mediated NF-kappa B activation in the NPC setting. These findings provide new insights into the mechanism underlying the deregulation of BARTs in NPC and identify a regulatory loop through which BARTs support EBV latency in NPC. |
收录类别 | SCI |
资助信息 | This work, including the efforts of Honglin Chen, was funded by The AreasofExcellenceSchemeoftheUniversityGrantsCommittee(AoE/M- 06/08). This work, including the efforts of Mei-Ru Chen, Jianji Pan, and HonglinChen,wasfundedbyTheCrossTraitJointFundsoftheNational Science Foundation of China (U1405221). |
语种 | 英语 |
源URL | [http://159.226.149.26:8080/handle/152453/10771] ![]() |
专题 | 昆明动物研究所_分子免疫药理学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
作者单位 | 1.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, People’s Republic of China 2.Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Provincial Clinical College of Fujian Medical University and Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, People’s Republic of China 3.National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian, People’s Republic of China 4.School of Biomedical Science, The University of Hong Kong, Hong Kong SAR, People’s Republic of China 5.Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taiwan 6.Present address: Gaohong Zhang, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People’s Republic of China. |
推荐引用方式 GB/T 7714 | Verhoeven RJA,Tong S,Jin DY,et al. NF-kappa B Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma[J]. JOURNAL OF VIROLOGY,2016,90(14):6475-6488. |
APA | Verhoeven RJA.,Tong S.,Jin DY.,Chen MR.,Pan JJ.,...&Chen YX[*].(2016).NF-kappa B Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma.JOURNAL OF VIROLOGY,90(14),6475-6488. |
MLA | Verhoeven RJA,et al."NF-kappa B Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma".JOURNAL OF VIROLOGY 90.14(2016):6475-6488. |
入库方式: OAI收割
来源:昆明动物研究所
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