MicroRNA-26a-mediated regulation of interleukin-2 expression in transformed avian lymphocyte lines

The expression levels of gga-miR-26a in chicken lymphoma cells transformed by 3 distinct avian oncogenic viruses, viz Marek's disease virus (MDV), avian leukosis virus (ALV) and Reticuloendotheliosis virus (REV) were consistently downregulated compared to the levels in the normal lymphocytes. This downregulation of miR-26a regardless of the viral etiology and molecular mechanisms of transformation was consistent with the tumor suppressor role of this miRNA. Notwithstanding this well-established role in cancer, we demonstrate the additional role of this miRNA in directly targeting chicken IL-2 through reporter and biochemical assays. The downregulation of miR-26a can relieve the suppressive effect of this miRNA on IL-2 expression.We show that miR-26a is globally downregulated in a number of avian lymphoma cells irrespective of the mechanisms of transformation, reiterating the highly conserved tumor suppressor function of this miRNA. However, with the potential for directly targeting chicken IL-2, the downregulation of miR-26a in these tumor cells could relieve the inhibitory effect on IL-2 expression assisting in the proliferative features of the transformed lymphocyte lines.Micro(mi)RNAs are a large class of ~22-nucleotide non-coding RNA molecules that participate a major part in the regulation of gene expression in majority of the eukaryotes. Increasingly, they have been shown to play significant roles in a variety of cancers, in particular of those involving different blood cells [1]. Marek's disease (MD), a naturally occurring CD4+ T-cell lymphoma in chickens induced by Marek's disease virus (MDV), is considered to be a very good model for herpesvirus-induced rapid-onset T-cell lymphomas [2]. Recent studies on the miRNA expression profiles of a number of MDV-transformed chicken lymphoid cell lines have shown significant alterations in the expression of several host miRNAs compared to the normal chicken lymphocytes [3]. One of the miRNAs that was consistently down