Expression of BamHI-A Rightward Transcripts in Epstein-Barr Virus-Associated Gastric Cancers
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Purpose About 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 Methods We 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 EBVassociated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions. Results Using 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 BamHIA 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. Conclusion BART 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.
Abstract
Purpose About 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 Methods We 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 EBVassociated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions. Results Using 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 BamHIA 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. Conclusion BART 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.
참고문헌 (22)
- Thompson MP, "Epstein-Barr virus and cancer", Clin Cancer Res, 10, pp.803~821 (2004)
- Takano Y, "The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas", Virchows Arch, 434, pp.17~22 (1999)
- Takada K, "Epstein-Barr virus and gastric carcinoma", Mol Pathol, 53, pp.255~261 (2000)
- Sugiura M, "Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells", Br J Cancer, 74, pp.625~631 (1996)
- zur Hausen A, "Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene", Cancer Res, 60, pp.2745~2748 (2000)
- Do Nyun Kim, "The role of promoter methylation in Epstein-Barr virus (EBV) microRNA expression in EBV-infected B cell lines", Experimental and Molecular Medicine, 43(7), pp.401~410 (2011), 생화학분자생물학회
- Lee JE, "MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits", Cell Prolif, 44, pp.59~66 (2011)
- Song LB, "Effect of EBV encoded BARF1 gene on malignant transformation of human epithelial cell line HBE", Ai Zheng, 23(11), pp.1361~1364 (2004)
- Wiech T, "Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer", Virchows Arch, 452, pp.621~627 (2008)
- "A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer", Virology, 320(2), pp.330~336
- Al-Mozaini M, "Epstein-Barr virus BART gene expression", J Gen Virol, 90, pp.307~316 (2009)
- Jung EJ, "Ganciclovir augments the lytic induction and apoptosis induced by chemotherapeutic agents in an Epstein-Barr virus-infected gastric carcinoma cell line", Anticancer Drugs, 18, pp.79~85 (2007)
- Hitt MM, "EBV gene expression in an NPC-related tumour", EMBO J, 8, pp.2639~2651 (1989)
- Smith PR, "Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus", J Virol, 74, pp.3082~3092 (2000)
- Zhang J, "Epstein-Barr virus BamHi-a rightward transcript- encoded RPMS protein interacts with the CBF1-associated corepressor CIR to negatively regulate the activity of EBNA2 and NotchIC", J Virol, 75, pp.2946~2956 (2001)
- Li A, "Transcriptional expression of RPMS1 in nasopharyngeal carcinoma and its oncogenic potential", Cell Cycle, 4, pp.304~309 (2005)
- Pfeffer S, "Identification of virusencoded microRNAs", Science, 304, pp.734~736 (2004)
- Edwards RH, "Epstein-Barr virus BART microRNAs are produced from a large intron prior to splicing", J Virol, 82, pp.9094~9106 (2008)
- Kim do N, "Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma", JOURNAL OF VIROLOGY, 81(2), pp.1033~1036 (2007)
- Barth S, "Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5", Nucleic Acids Res, 36, pp.666~675 (2008)
- Lo AK, "Modulation of LMP1 protein expression by EBV-encoded microRNAs", Proc Natl Acad Sci U S A, 104, pp.16164~16169 (2007)
- Choy EY, "An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival", J Exp Med, 205, pp.2551~2560 (2008)
