EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3

The Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Cancer Research (Impact Factor: 9.33). 04/2008; 68(5):1436-42. DOI: 10.1158/0008-5472.CAN-07-5126
Source: PubMed


EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated non-Hodgkin's lymphomas is unknown. We analyzed five primary "endemic" pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV(+) primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs. A markedly elevated expression of miRNA BHRF1-3 in type III relative to its parental type I BL line was found. Primary unmanipulated type I BLs and EBV(+) PELs expressed high levels of BART2 miRNA, whereas DLBCLs expressed both BART2 and BHRF1-3 species. BHRF1-3 miRNA expression inversely correlated with levels of a putative cellular target, the IFN-inducible T-cell attracting chemokine CXCL-11/I-TAC, and suppression of this factor was reversed by transfection of an antisense oligo to the EBV miRNA BHRF1-3. EBV-encoded miRNAs are expressed in primary lymphomas classically linked to the virus and are associated with the viral latency status. Targeted suppression of CXCL-11/I-TAC by a viral-encoded miRNA may serve as an immunomodulatory mechanism in these tumors.

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Available from: Ngoc Toomey, Apr 29, 2014
    • "During the early phase of B cell infection , BHRF1 microRNAs may induce apoptosis resistance and cell proliferation (Seto et al. 2010 ). In primary lymphomas exhibiting latency type III, miR-BHRF1-3 may contribute to the downregulation of the T cell attracting chemokine CXCL11 (Xia et al. 2008 ). "
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    • "Several virus-encoded miRNAs have been reported to target host transcripts for their own advantage. There are reports of viral miRNAs targeting antiviral signaling molecules, e.g., EBV encoded miR-BHRF1-3 downregulates CXC-chemokine ligand 11 (CXCL11), an interferon (IFN)-inducible T-cell chemoattractant (Xia et al., 2008). The host gene Thrombospondin 1 (THBS1) has been reported to be targeted by multiple KSHV miRNAs, identified through gene expression profiling of cells engineered to stably express 10 KSHV pre-miRNAs (Samols et al., 2007). "
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