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Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma

 Seung Myung Dong  ;  Hyun Gyu Lee  ;  Sung Gyu Cho  ;  Seung Hyun Kwon  ;  Heejei Yoon  ;  Hyun Jin Kwon  ;  Ji Hae Lee  ;  Hyemi Kim  ;  Pil Gu Park  ;  Hoguen Kim  ;  S. Diane Hayward  ;  Jeon Han Park  ;  Jae Myun Lee 
 Journal of Microbiology, Vol.53(1) : 70-76, 2015 
Journal Title
 Journal of Microbiology 
Issue Date
Interferon regulatory factor-5 (IRF-5), a member of the mammalian IRF transcription factor family, is regulated by p53, type I interferon and virus infection. IRF-5 participates in virus-induced TLR-mediated innate immune responses and may play a role as a tumor suppressor. It was suppressed in various EBV-infected transformed cells, thus it is valuable to identify the suppression mechanism. We focused on a promoter CpG islands methylation, a kind of epigenetic regulation in EBV-associated Burkitt's lymphomas (BLs) and gastric carcinomas. IRF-5 is not detected in most of EBV-infected BL cell lines due to hypermethylation of IRF-5 distal promoter (promoter-A), which was restored by a demethylating agent, 5-aza-2'-deoxycytidine. Hypomethylation of CpG islands in promoter-A was observed only in EBV type III latent infected BL cell lines (LCL and Mutu III). Similarly, during EBV infection to Akata-4E3 cells, IRF-5 was observed at early time periods (2 days to 8 weeks), concomitant unmethylation of promoter-A, but suppressed in later infection periods as observed in latency I BL cell lines. Moreover, hypermethylation in IRF-5 promoter-A region was also observed in EBV-associated gastric carcinoma (EBVaGC) cell lines or primary gastric carcinoma tissues, which show type I latent infection. In summary, IRF-5 is suppressed by hypermethylation of its promoter-A in most of EBV-infected transformed cells, especially BLs and EBVaGC. EBV-induced carcinogenesis takes an advantage of proliferative effects of TLR signaling, while limiting IRF-5 mediated negative effects in the establishment of EBVaGCs.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
권승현(Kwon, Seung Hyun)
권현진(Kwon, Hyun Jin)
김호근(Kim, Ho Keun)
박전한(Park, Jeon Han) ORCID logo https://orcid.org/0000-0001-9604-3205
박필구(Park, Pil Gu) ORCID logo https://orcid.org/0000-0002-3024-3439
이재면(Lee, Jae Myun) ORCID logo https://orcid.org/0000-0002-5273-3113
이현규(Lee, Hyun Gyu)
조성규(Cho, Sung Gyu)
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