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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalJournal of Microbiology
Volume53
Issue number1
DOIs
StatePublished - Jan 17 2015

Keywords

  • CpG island
  • Epstein-Barr virus
  • gastric carcinoma
  • interferon regulatory factor 5
  • promoter methylation

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

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