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Epstein-Barr virus BALF3 mediates genomic instability and progressive malignancy in nasopharyngeal carcinoma

2014; Impact Journals LLC; Volume: 5; Issue: 18 Linguagem: Inglês

10.18632/oncotarget.2323

1949-2553

Shih-Hsin Chiu, Chung-Chun Wu, Chih‐Yeu Fang, Shu‐Ling Yu, Hui‐Yu Hsu, Yen‐Hung Chow, Jen‐Yang Chen,

RNA modifications and cancer

// Shih-Hsin Chiu 1 , 2 , Chung-Chun Wu 2 , Chih-Yeu Fang 2 , Shu-Ling Yu 3 , Hui-Yu Hsu 2 , Yen-Hung Chow 3 , Jen-Yang Chen 1 , 2 1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 2 National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan 3 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan Correspondence to: Jen-Yang Chen, email: cjy@nhri.org.tw Keywords: nasopharyngeal carcinoma, relapse, Epstein-Barr virus, BALF3, genomic instability Received: April 20, 2014 Accepted: August 05, 2014 Published: August 10, 2014 ABSTRACT Nasopharyngeal carcinoma (NPC) is a head and neck cancer prevalent throughout Southern China and Southeast Asia. Patient death following relapse after primary treatment remains all too common but the cause of NPC relapse is unclear. Clinical and epidemiological studies have revealed the high correlation among NPC development, Epstein-Barr virus (EBV) reactivation and host genomic instability. Previously, recurrent EBV reactivation was shown to cause massive genetic alterations and enhancement of tumor progression in NPC cells and these may be required for NPC relapse. Here, EBV BALF3 has the ability to induce micronuclei and DNA strand breaks. After recurrent expression of BALF3 in NPC cells, genomic copy number aberrations, determined by array-based comparative genomic hybridization, had accumulated to a significant extent and tumorigenic features, such as cell migration, cell invasion and spheroid formation, increased with the rounds of induction. In parallel experiments, cells after highly recurrent induction developed into larger tumor nodules than control cells when inoculated into NOD/SCID mice. Furthermore, RNA microarrays showed that differential expression of multiple cancer capability-related genes and oncogenes increased with recurrent BALF3 expression and these changes correlated with genetic aberrations. Therefore, EBV BALF3 is a potential factor that mediates the impact of EBV on NPC relapse.