title: Dissecting the regulation of EBV's BART miRNAs in carcinomas.
abstract: Epstein-Barr virus (EBV) encodes multiple miRNAs known to contribute to its pathogenicity. Previous studies have found that the levels of some EBV miRNAs are 10-100 fold higher in biopsies and in tumor xenografts than in cells grown in culture. We have asked if these increased levels reflect transcriptional enhancement resulting from the tumor microenvironment, selection for increased levels of the EBV genome, or both. We measured the levels of BART miRNAs and their DNA templates in tumor xenografts induced from EBV-positive gastric carcinoma cells and EBV-negative gastric carcinoma cells expressing plasmid replicons encoding these miRNAs. We focused on BART miRNAs which are expressed in all tumors and found that they provide tumors selective growth advantages as xenografts. Stem-loop PCR and real-time PCR revealed that the xenografts expressed both higher levels of some miRNAs and viral DNA templates than did the corresponding cells in culture.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705-2275, United States.
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Yang
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705-2275, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Liem
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705-2275, United States.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705-2275, United States. Electronic address: sugden@oncology.wisc.edu.
authors.forename: Bill
authors.initials: B
authors.lastname: Sugden
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs
keywords: BamHI A rightward transcripts; Epstein-Barr virus; Micro RNAs