Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation

文献类型： 外文期刊

第一作者： Yao, Yongxiu

作者： Yao, Yongxiu;Kgosana, Lydia;Smith, Lorraine P.;Nair, Venugopal;Yao, Yongxiu;Kgosana, Lydia;Smith, Lorraine P.;Nair, Venugopal;Vasoya, Deepali;Watson, Mick;Vasoya, Deepali;Watson, Mick;Gao, Yulong;Wang, Xiaomei

作者机构：

关键词： v-rel;NF-kappa B;miR-155;transformation

期刊名称：JOURNAL OF GENERAL VIROLOGY （ 影响因子：3.891； 五年影响因子：3.719 ）

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收录情况： SCI

摘要： The v-rel oncoprotein encoded by reticuloendotheliosis virus T strain (Rev-T) is a member of the rel/NF-kappa B 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-kappa B 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 CEBP beta. 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-kappa B targets, together with inhibitory effects on microRNA targets.

分类号： R37

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