Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8.
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.
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
Y
Y
Jiang
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
B
B
Yan
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
W
W
Lai
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
Y
Y
Shi
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
D
D
Xiao
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
J
J
Jia
Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
S
S
Liu
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
H
H
Li
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
J
J
Lu
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Z
Z
Li
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
L
L
Chen
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
X
X
Chen
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China.
L
L
Sun
Mouse Cancer Genetics Program, National Cancer Institute, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
K
K
Muegge
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
Y
Y
Cao
Cancer Research Institute, Central South University, Changsha, Hunan, China.|Center for Molecular Imaging, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
Y
Y
Tao
D002478:Cells, Cultured; D002952:Citric Acid Cycle; D019175:DNA Methylation; D049308:Dioxygenases / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D006019:Glycolysis; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D014763:Viral Matrix Proteins; C578792:TET3 protein, human; D049308:Dioxygenases; D012319:RNA Polymerase II