a novel persistence associated ebv mirna expression profile is disrupted in neoplasia一种新型持久性ebv相关microrna的表达谱在肿瘤破坏.pdfVIP

A Novel Persistence Associated EBV miRNA Expression Profile Is Disrupted in Neoplasia 1 1 2 2 3 2 Jin Qiu , Katherine Cosmopoulos , Michiel Pegtel , Erik Hopmans , Paul Murray , Jaap Middeldorp , 1 1 Michael Shapiro , David A. Thorley-Lawson * 1 Dept of Pathology, Tufts University School of Medicine, Boston, Massachusetts, United States of America, 2 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands, 3 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom Abstract We have performed the first extensive profiling of Epstein-Barr virus (EBV) miRNAs on in vivo derived normal and neoplastic infected tissues. We describe a unique pattern of viral miRNA expression by normal infected cells in vivo expressing restricted viral latency programs (germinal center: Latency II and memory B: Latency I/0). This includes the complete absence of 15 of the 34 miRNAs profiled. These consist of 12 BART miRNAs (including approximately half of Cluster 2) and 3 of the 4 BHRF1 miRNAs. All but 2 of these absent miRNAs become expressed during EBV driven growth (Latency III). Furthermore, EBV driven growth is accompanied by a 5–10 fold down regulation in the level of the BART miRNAs expressed in germinal center and memory B cells. Therefore, Latency III also expresses a unique pattern of viral miRNAs. We refer to the miRNAs that are specifically expressed in EBV driven growth as the Latency III associated miRNAs. In EBV associated tumors that employ Latency I or II (Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma and gastric carcinoma), the Latency III assoc