Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8

• Published in: Oncogene 2015-12, Vol.34 (50), p.6079-6091
• Main Authors: Jiang, Y, Yan, B, Lai, W, Shi, Y, Xiao, D, Jia, J, Liu, S, Li, H, Lu, J, Li, Z, Chen, L, Chen, X, Sun, L, Muegge, K, Cao, Y, Tao, Y
• Format: Article
• Language: English
• Subjects: 631/67/1858; Apoptosis; Cell Biology; Cell immortalization; Cells, Cultured; Citric Acid Cycle; Development and progression; Dioxygenases - physiology; DNA Methylation; DNA-directed RNA polymerase; Ectopic expression; Epstein-Barr virus; Gene expression; Gene silencing; Genes, Homeobox - physiology; Genetic aspects; Glycolysis; Health aspects; Homeodomain Proteins - physiology; HOX gene; Human Genetics; Humans; Immortalization; Internal Medicine; Kinases; Latency; Latent membrane protein 1; Lymphocytes; Medicine; Medicine & Public Health; Membrane proteins; Membranes; Nasopharyngeal cancer; Nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Oncology; original-article; Proteins; Radiation; RNA polymerase; RNA Polymerase II - metabolism; Throat cancer; Tricarboxylic acid cycle; Tumor cell lines; Viral Matrix Proteins - physiology; Viruses
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/onc.2015.53

Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte-specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA polymerase II (RNA Pol II). Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, has a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo , modulates glycolysis and regulates the expression of tricarboxylic acid (TCA) cycle-related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis.