Ten EBVaGC tumor samples were used to analyze the expression of BARF1 and BHRF1.
BARF1 and BHRF1 are silenced by methylation in EBVaGC. However, the association of BARF1 and BHRF1 with EBVaGC carcinogenesis was still in question.
(b) Expression level of BARF1 and BHRF1 in EBVaGC samples.
The latency pattern in EBVaGCs belongs to either latency I or II, which expresses EBER, EBNA1, BART, LMP2A, and BART miRNAs [1,4,5].
102 EBVaGCs were screened out and 43 cases were used in this study.
Especially in EBV-positive GC, BARF1 is expressed in the absence of LMP1, possibly functioning as an EBV oncogene in this disease and playing an important role in the occurrence and development of EBVaGCs [12,14,16].
In this study, we explored the CpG methylation profiles of EBV early genes BARF1 and BHRF1 in EBV-positive cell lines and EBVaGCs tissues by MSP and BSP and further evaluated the promoter CpG methylation and their mRNA expression before and after 5-Aza-CdR treatment.
Further studies also confirmed that abnormal DNA methylation in the promoter regions of the gene, which provides inactivation of tumor suppressor and other cancer-related genes, is the most well-defined epigenetic characteristic in EBVaGC but not in EBV nonassociated GC (EBVnGC) [11, 60-66].
Increasing evidence suggests that EBV is a DNA tumor virus belonging to the human gamma-herpesvirus family, which is capable of establishing a latent infection mainly in human B lymphocytes and epithelial cells, and is associated with several human lymphoid and epithelial cell malignancies including EBVaGC [1-6].
EBVaGC is characterized by unique clinical and pathologic features including male predominance, the presence of EBV genomes and EBV-encoded small RNA (EBER) in gastric carcinoma cell lines, and monoclonal proliferation of EBV-infected carcinoma cells [4, 9, 57, 104].
In addition, these viral miRNAs incorporated into RISC complex can also interact directly with specific host genes involved in immune surveillance, cell proliferation, and apoptosis, playing a crucial role in the aetiology of diverse diseases including EBVaGC.
Shinozaki-Ushiku et In the present review latest al., 2015 findings on EBVaGC from clinicopathological and molecular perspectives were discussed to provide a better understanding of EBV involvement in gastric carcinogenesis.