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

Oncogene volume 34, pages 6079–6091 (2015)Cite this article

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Abstract

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.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2011CB504300 (YT); 2015CB553903 (YT)); the Hunan Natural Science Foundation of China (12JJ1013 (YT)); the Fundamental Research Funds for the Central Universities (2011JQ019 (YT), 2013ZZTS074 (BY), 2013ZZTS284 (WL)); and the National Natural Science Foundation of China (81171881 and 81372427 (YT), 81271763 (SL), 81302354 (YS)); and the Hunan Provincial Innovation Foundation For Postgraduate (71380100002 (YJ)). This project has been funded in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

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  1. B Yan, W Lai and Y Shi: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Research Institute, Central South University, Changsha, Hunan, China

    Y Jiang, B Yan, W Lai, Y Shi, J Jia, H Li, J Lu, L Chen, X Chen, Y Cao & Y Tao

  2. Center for Molecular Imaging, Central South University, Changsha, Hunan, China

    Y Jiang, B Yan, W Lai, Y Shi, H Li, J Lu, L Chen, X Chen, Y Cao & Y Tao

  3. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China

    Y Jiang, B Yan, W Lai, Y Shi, H Li, J Lu, L Chen, X Chen, Y Cao & Y Tao

  4. Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China

    Y Jiang, B Yan, W Lai, Y Shi, H Li, J Lu, L Chen, X Chen, Y Cao & Y Tao

  5. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    D Xiao

  6. Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China

    J Jia & S Liu

  7. Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China

    Z Li & L Sun

  8. Mouse Cancer Genetics Program, National Cancer Institute, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    K Muegge

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Jiang, Y., Yan, B., Lai, W. et al. Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8. Oncogene 34, 6079–6091 (2015). https://doi.org/10.1038/onc.2015.53

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