title: Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation.
abstract: The v-rel oncoprotein encoded by reticuloendotheliosis virus T strain (Rev-T) is a member of the rel/NF-κB family of transcription factors capable of transformation of primary chicken spleen and bone marrow cells. Rapid transformation of avian haematopoietic cells by v-rel occurs through a process of deregulation of multiple protein-encoding genes through its direct effect on their promoters. More recently, upregulation of oncogenic miR-155 and its precursor pre-miR-155 was demonstrated in both Rev-T-infected chicken embryo fibroblast cultures and Rev-T-induced B-cell lymphomas. Through electrophoresis mobility shift assay and reporter analysis on the gga-miR-155 promoter, we showed that the v-rel-induced miR-155 overexpression occurred by the direct binding to one of the putative NF-κB binding sites. Using the v-rel-induced transformation model on chicken embryonic splenocyte cultures, we could demonstrate a dynamic increase in miR-155 levels during the transformation. Transcriptome profiles of lymphoid cells transformed by v-rel showed upregulation of miR-155 accompanied by downregulation of a number of putative miR-155 targets such as Pu.1 and CEBPβ. We also showed that v-rel could rescue the suppression of miR-155 expression observed in Marek's disease virus (MDV)-transformed cell lines, where its functional viral homologue MDV-miR-M4 is overexpressed. Demonstration of gene expression changes affecting major molecular pathways, including organismal injury and cancer in avian macrophages transfected with synthetic mature miR-155, underlines its potential direct role in transformation. Our study suggests that v-rel-induced transformation involves a complex set of events mediated by the direct activation of NF-κB targets, together with inhibitory effects on microRNA targets.
authors.affiliation: Avian Viral Disease Programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.
authors.forename: Yongxiu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Deepali
authors.initials: D
authors.lastname: Vasoya
authors.affiliation: Avian Viral Disease Programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kgosana
authors.affiliation: Avian Viral Disease Programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Smith
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Mick
authors.initials: M
authors.lastname: Watson
authors.affiliation: Avian Viral Disease Programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Nair
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002645:Chickens; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007963:Leukocytes, Mononuclear / Q000821:virology; D020572:Oncogene Proteins v-rel / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis*; D001356:Reticuloendotheliosis virus / Q000472:pathogenicity*
chemical_list: D020572:Oncogene Proteins v-rel; D012333:RNA, Messenger