The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq - Université de Tours Accéder directement au contenu
Article Dans Une Revue Journal of Virology Année : 2013

The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq

Résumé

Gallid herpesvirus 2 (GaHV-2) is an oncogenic herpesvirus that causes T lymphoma in chicken. GaHV-2 encodes a basic leucine zipper (bZIP) protein of the AP-1 family, Meq. Upon formation of homo- or heterodimers with c-Jun, Meq may modulate the expression of viral and cellular genes involved in lymphomagenesis. GaHV-2 also encodes viral microRNAs (miRNAs) involved in latency and apoptosis escape. However, little is known about cellular miRNA deregulation during the development of GaHV-2-associated lymphoma. We determined the cellular miRNA expression profiles of chickens infected with a very virulent strain (RB-1B) or a vaccine strain (CVI988) or noninfected. Among the most deregulated cellular miRNAs, we focused our efforts on gga-miR-21, which is upregulated during GaHV-2 infection. We mapped the gga-miR-21 promoter to the 10th intron of the TMEM49 gene and found it to be driven by AP-1- and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. Finally, gga-miR-21 was overexpressed only during infection with a very virulent strain (RB-1B) and not during infection with a nononcogenic strain (CVI988), providing further evidence for its role in GaHV-2 lymphomagenesis. Our data therefore suggest an additional role for Meq in GaHV-2-mediated lymphomagenesis through the induction of miR-21 expression.

Domaines

Virologie

Dates et versions

hal-02650981 , version 1 (29-05-2020)

Identifiants

Citer

Gregoire Stik, Ginette Dambrine, Sébastien Pfeffer, Denis Rasschaert. The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq. Journal of Virology, 2013, 87 (1), pp.80-93. ⟨10.1128/JVI.02449-12⟩. ⟨hal-02650981⟩
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