Müller Coan Barbara G, Cesarman Ethel, Acencio Marcio Luis, Elgui de Oliveira Deilson
Biosciences Institute of Botucatu, São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Genes (Basel). 2022 Feb 16;13(2):353. doi: 10.3390/genes13020353.
The Epstein-Barr virus (EBV) is a ubiquitous γ herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ in cell tropism and the activation of the lytic cycle. Nonetheless, it is unknown whether LMP1 from these strains have different effects when expressed in nasopharyngeal cells. Thus, herein we evaluated the effects of EBV LMP1 derived from viral strains B95.8 and M81 and expressed in immortalized nasopharyngeal cells NP69 in the regulation of 91 selected cellular miRNAs. We found that cells expressing either LMP1 behave similarly in terms of NF-kB activation and cell migration. Nonetheless, the miRs 100-5p, 192-5p, and 574-3p were expressed at higher levels in cells expressing LMP1 B95.8 compared to M81. Additionally, results generated by in silico pathway enrichment analysis indicated that LMP1 M81 distinctly regulate genes involved in cell cycle (i.e., ), mRNA processing (i.e., ), and mitochondrial biogenesis (i.e., ). In conclusion, LMP1 M81 was found to distinctively regulate miRs 100-5p, 192-5p, and 574-3p, and the in silico analysis provided valuable clues to dissect the molecular effects of EBV LMP1 expressed in nasopharyngeal cells.
爱泼斯坦-巴尔病毒(EBV)是一种普遍存在的γ疱疹病毒,与鼻咽癌密切相关,其病毒致癌性部分依赖于病毒潜伏膜蛋白1(LMP1)的细胞效应。此前有描述称,EBV毒株B95.8和M81在细胞嗜性和裂解周期激活方面存在差异。然而,这些毒株的LMP1在鼻咽细胞中表达时是否具有不同作用尚不清楚。因此,在本文中,我们评估了源自病毒毒株B95.8和M81并在永生化鼻咽细胞NP69中表达的EBV LMP1对91种选定细胞miRNA的调控作用。我们发现,表达任一LMP1的细胞在NF-κB激活和细胞迁移方面表现相似。然而,与表达LMP1 M81的细胞相比,miR 100-5p、192-5p和574-3p在表达LMP1 B95.8的细胞中表达水平更高。此外,通过计算机通路富集分析得出的结果表明,LMP1 M81对参与细胞周期(即 )、mRNA加工(即 )和线粒体生物发生(即 )的基因有明显调控作用。总之,我们发现LMP1 M81对miR 100-5p、192-5p和574-3p有独特的调控作用,计算机分析为剖析在鼻咽细胞中表达的EBV LMP1的分子效应提供了有价值的线索。