LMP1 stimulates the transcription of eIF4E to promote the proliferation, migration and invasion of human nasopharyngeal carcinoma.

Abstract

Eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting translation initiation factor for many oncogenes. Previous studies have shown eIF4E overexpression in nasopharyngeal carcinoma (NPC). We aimed to study whether viral oncogene latent membrane protein 1 (LMP1) stimulates the transcription of eIF4E to promote NPC malignancy. In NPC cell lines (CNE1 and CNE2), ectopic LMP1 significantly increased the mRNA and protein levels of eIF4E and the transcriptional activity of the eIF4E promoter in a LMP1-plasmid-transfected dose-dependent manner. As a backward experiment, knocking down of LMP1 significantly reduced eIF4E mRNA in B95-8 cells. In the high LMP1 expression condition, knocking down of c-Myc significantly reduced eIF4E mRNA in both NPC and B95-8 cells, and knocking down of eIF4E significantly inhibited the tumor proliferation, migration and invasion promoted by LMP1. The results indicated that LMP1 stimulates the transcription of eIF4E via c-Myc to promote NPC. To the best of our knowledge, this is the first evidence that LMP1 stimulates the transcription of eIF4E. This might be an important cause of the overexpression of eIF4E in NPC and be the novel mechanism by which LMP1 initiates cancer. LMP1-stimulated eIF4E initiates the translation of those oncogenes transcriptionally activated by LMP1 to amplify and pass down the carcinogenesis signals launched by LMP1.

• Authors: Yi Zhao, Tian-Yun Pang, Yan Wang, Sen Wang, Hai-Xian Kang, Wei-Bin Ding, Wei-Wei Yong, Yan-Hong Bie, Xiao-Guang Cheng, Chao Zeng, Yun-Hong Yao, Qing Li, Xin-Rong Hu
• Journal: The FEBS journal (FEBS J) Vol. 281 Issue 13 Pg. 3004-18 (Jul 2014) ISSN: 1742-4658 [Electronic] England
• PMID: 24814906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 FEBS.

Chemical References

• EBV-associated membrane antigen, Epstein-Barr virus
• Eukaryotic Initiation Factor-4E
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• RNA, Small Interfering
• Viral Matrix Proteins

Topics

• Carcinoma
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epstein-Barr Virus Infections (metabolism, pathology)
• Eukaryotic Initiation Factor-4E (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Host-Pathogen Interactions
• Humans
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (metabolism, pathology, virology)
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Transcriptional Activation
• Viral Matrix Proteins (physiology)