Expression of BamHI-A Rightward Transcripts in Epstein-Barr Virus-Associated Gastric Cancers

Abstract

PurposeAbout 10% of all gastric cancers (GCs) are Epstein-Barr virus (EBV)-associated. However, the oncogene of EBV in gastric carcinogenesis has not yet been established. In the present study, we investigated the virus-derived transcripts in the EBV-infected GC cell line to explore the viral oncogene of EBV-positive GCs.Materials and MethodsWe used the SNU719 cell line, a naturally derived EBV-infected GC cell line. The individual expressed sequence tags from the cDNA libraries of SNU719 were searched against the mRNA subset extracted from the GenBank data base. Sequence reaction was carried out for the EBV-associated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions.ResultsUsing bioinformatic tools, we selected 13 EBV-associated clones from cDNA libraries of SNU719. By sequencing analysis, we revealed that they were all associated with RPMS1, one of the BamHI-A rightward transcripts (BART) of EBV. Some BART cDNAs such as RPMS1 and A73 are known to be translated into protein in vitro, and have been shown to have some biochemical functions relevant to tumorigenesis. But, presently, the BART transcripts were expressed only in the nucleus and not in the cytoplasm, arguing against their role as messenger RNAs. Some other BART transcripts expressed in GCs (BARF0, CST, vIL, BARF1, BLLF1, and BcLF1) were also extensively detected in the nucleus.ConclusionBART transcripts are the predominant viral transcripts expressed in EBV-associated GCs, and they are located only in the nucleus. Therefore, it seems less likely that BART transcripts produce functional proteins to play a role in carcinogenesis of EBV-associated GCs.

Differences in Gastric Carcinoma Microenvironment Stratify According to EBV Infection Intensity: Implications for Possible Immune Adjuvant Therapy

“…The magnitude of expression from the BamHI A region relative to the transcription levels of other EBV genes is striking, however. This result is consistent with a previous report using a naturally infected EBV positive gastric carcinoma cell line [26]. Nevertheless, our analysis makes this observation in the natural in vivo setting of the tumor, and the use of RNA-seq facilitated the evaluation of transcript structures and the magnitudes of BamHI A region gene expression relative to other viral and cellular genes.…”

Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

“…BNLF-2A , detected in a significant number of our cases, may protect infected B-cells from immune recognition and elimination[ 53 ]. Finally, the EBV transcriptome during the reactivation may involve the contribution of a wide array of other virus-encoded RNAs, such as BARF-0, BARF-1, BcLF-1, and RPMSI-1[ 54 ], that are not translated and may function as non-coding RNA molecules which could participate in regulating gene expression[ 55 ]. Heterogeneity in lytic/latent expression programs can be observed not only between patients but also within individual tumors, on a cell-to-cell basis.…”

Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

“…As noted above, significant progress has occurred in the past decade in characterizing effects of EBV on host cell-encoded immunoregulatory microRNA [ 8 – 16 ] and also expression of viral-encoded noncoding and microRNA [ 17 – 26 ]. However, the author and others have previously suggested that much of the immunopathology associated with EBV infection may involve “hit-and-run” effects of EBV gene products transiently expressed in noninfected bystander cells [ 32 ].…”

“…The author has also previously suggested that EBV may also potentially affect the biology bystander cells such as T lymphocytes through a variety of mechanisms in autoimmune syndromes such as systemic lupus erythematosus (SLE) which are related to EBV infection based on epidemiologic evidence [ 7 ]. Since numerous recent publications confirm that viral-encoded microRNA have a complex relationship with host-encoded immunoregulatory microRNA [ 8 – 16 ], and viral-encoded microRNA are themselves apparently coregulated by host and viral immune response transcription factors [ 17 – 26 ], it is reasonable to include viral and host microRNA in the “shared gene paradigm.”…”