Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation.
J Gen Virol
; 98(4): 810-820, 2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-28113043
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 CEBPß. 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Transformação Celular Viral
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Vírus da Reticuloendoteliose
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Proteínas Oncogênicas v-rel
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Interações Hospedeiro-Patógeno
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Gen Virol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido