LMP 1 stimulates the transcription of e IF 4E to promote the proliferation, migration and invasion of human nasopharyngeal carcinoma

• Published in: The FEBS journal 2014-07, Vol.281 (13), p.3004-3018
• Main Authors: Zhao, Yi, Pang, Tian‐yun, Wang, Yan, Wang, Sen, Kang, Hai‐xian, Ding, Wei‐bin, Yong, Wei‐wei, Bie, Yan‐hong, Cheng, Xiao‐guang, Zeng, Chao, Yao, Yun‐hong, Li, Qing, Hu, Xin‐rong
• Format: Article
• Language: English
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12838

Eukaryotic translation initiation factor 4E (e IF 4E) is the rate‐limiting translation initiation factor for many oncogenes. Previous studies have shown e IF 4E overexpression in nasopharyngeal carcinoma ( NPC ). We aimed to study whether viral oncogene latent membrane protein 1 ( LMP 1) stimulates the transcription of e IF 4E to promote NPC malignancy. In NPC cell lines ( CNE 1 and CNE 2), ectopic LMP 1 significantly increased the m RNA and protein levels of e IF 4E and the transcriptional activity of the e IF 4E promoter in a LMP 1–plasmid‐transfected dose‐dependent manner. As a backward experiment, knocking down of LMP 1 significantly reduced e IF 4E m RNA in B95‐8 cells. In the high LMP 1 expression condition, knocking down of c‐Myc significantly reduced e IF 4E m RNA in both NPC and B95‐8 cells, and knocking down of e IF 4E significantly inhibited the tumor proliferation, migration and invasion promoted by LMP 1. The results indicated that LMP 1 stimulates the transcription of e IF 4E via c‐Myc to promote NPC . To the best of our knowledge, this is the first evidence that LMP 1 stimulates the transcription of e IF 4E. This might be an important cause of the overexpression of e IF 4E in NPC and be the novel mechanism by which LMP 1 initiates cancer. LMP 1‐stimulated e IF 4E initiates the translation of those oncogenes transcriptionally activated by LMP 1 to amplify and pass down the carcinogenesis signals launched by LMP 1.