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Abstract / Description of output
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 were demonstrated in Rev-T-infected chicken embryo fibroblast cultures as well as Rev-T-induced B-cell lymphomas. Through electrophoresis mobility shift assay and reporter analysis on gga-miR-155 promoter, we show that the v-rel-induced miR- 155 overexpression occurs by the direct binding to one of the putative NF-κB binding sites. Using v-rel-induced transformation model on chicken embryonic splenocyte cultures, we could demonstrate 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 show that v-rel can rescue the suppression of miR-155 expression observed in Marek’s disease virus-transformed cell lines, where its functional viral homolog 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 underline its potential direct role in transformation. Our study suggests that v-rel-induced transformation involves complex set of events mediated by the direct activation of NF-κB targets together with the inhibitory effects on miRNA targets.
Original language | English |
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Journal | Journal of General Virology |
Early online date | 22 Jan 2017 |
DOIs | |
Publication status | E-pub ahead of print - 22 Jan 2017 |
Keywords / Materials (for Non-textual outputs)
- v-rel
- NF-κB
- miR-155
- transformation
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Dive into the research topics of 'Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation'. Together they form a unique fingerprint.Projects
- 4 Finished
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ISP4 Pathogenesis and resistance in viral diseases of livestock
Dutia, B., Archibald, A., Beard, P., Bishop, S., Bronsvoort, M., Burt, D., Collie, D., Digard, P., Freeman, T., Glass, E., Grey, F., Hocking, P., Houston, R., Hume, D., Kaiser, P., Nash, A., Sang, H., Sharp, C., Watson, M. & Whitelaw, B.
1/04/12 → 31/03/17
Project: Research