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MicroRNAs 221 and 222 target p27^Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

¹ Institute for Animal Helath;
² Institute for Animal Health

³ E-mail: venu.gopal{at}bbsrc.ac.uk

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 p27Kip1. 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 are being increasingly recognised. 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 p27Kip1 3'UTR sequence and the repression of luciferase activity of reporter constructs indicated that miR-221 and miR-222 target p27Kip1 in these cells. We also found that the over-expression of miR-221 and miR-222 decreased p27Kip1 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 p27Kip1 in the induction and progression of T cell lymphomas.

Received 8 October 2008; accepted 16 January 2009.

This article has been cited by other articles:

				Y. Yao, Y. Zhao, L. P. Smith, C. H. Lawrie, N. J. Saunders, M. Watson, and V. Nair Differential expression of microRNAs in Marek's disease virus-transformed T-lymphoma cell lines J. Gen. Virol., July 1, 2009; 90(7): 1551 - 1559. [Abstract] [Full Text] [PDF]