title: MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1.
abstract: MicroRNAs (miRNAs) are a class of short RNAs that function as post-transcriptional suppressors of protein expression and are involved in a variety of biological processes, including oncogenesis. Several recent studies have implicated the involvement of miR-221 and miR-222 in tumorigenesis as these miRNAs are upregulated in a number of cancers and affect the expression of cell cycle regulatory proteins such as the cyclin-dependent kinase (cdk) inhibitor p27(Kip1). Marek's disease virus (MDV) is a highly oncogenic herpesvirus that affects poultry, causing acute neoplastic disease with lymphomatous lesions in several organs. MDV-encoded oncogenes such as Meq are directly implicated in the neoplastic transformation of T cells and have been well studied. More recently, however, the involvement of both host and virus-encoded miRNAs in the induction of MD lymphomas is being increasingly recognized. We analysed the miRNA expression profiles in the MDV-transformed lymphoblastoid cell line MSB-1 and found that endogenous miRNAs miR-221 and miR-222 were significantly upregulated. Demonstration of the conserved binding sites for these miRNAs in the chicken p27(Kip1) 3'-untranslated region sequence and the repression of luciferase activity of reporter constructs indicated that miR-221 and miR-222 target p27(Kip1) in these cells. We also found that overexpression of miR-221 and miR-222 decreased p27(Kip1) levels and that treatment with retrovirally expressed antagomiRs partially alleviated this suppression. These data show that an oncogenic herpesvirus, as in the case of many cancers, can exploit the miRNA machinery for suppressing cell cycle regulatory molecules such as p27(Kip1) in the induction and progression of T-cell lymphomas.
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Lambeth
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
authors.forename: Yongxiu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Smith
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Jenner Institute, University of Oxford, Compton, Berkshire RG20 7NN, UK.|Division of Microbiology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Nair
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002645:Chickens; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D025922:Mardivirus / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D013047:Specific Pathogen-Free Organisms
chemical_list: D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27