Overexpression of cellular telomerase RNA enhances virus-induced cancer formation.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
17
04
2018
accepted:
25
09
2018
revised:
28
08
2018
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
15
5
2019
Statut:
ppublish
Résumé
The telomerase RNA subunit (TR) is overexpressed in many tumors; however, the contribution of TR in cancer formation remains elusive. The most frequent clinically diagnosed cancer in the animal kingdom is caused by the highly oncogenic herpesvirus Marek's disease virus (MDV). MDV encodes a TR (vTR) that plays an important role in virus-induced tumorigenesis and shares 88% sequence identity with its cellular homologue. To determine if the cellular TR possesses pro-oncogenic activity, we replaced vTR with the cellular homologue in the virus genome. Insertion of cellular TR resulted in a strong overexpression in virus infected cells, while virus replication was not affected. Strikingly, cellular TR promoted tumor formation as efficient as vTR, while tumorigenesis was severely impaired in the absence of vTR. Our data provide the first evidence that overexpression of cellular TR can contribute to tumor formation in vivo using this natural virus-host model for herpesvirus-induced oncogenesis.
Identifiants
pubmed: 30846849
doi: 10.1038/s41388-018-0544-1
pii: 10.1038/s41388-018-0544-1
doi:
Substances chimiques
telomerase RNA
0
RNA
63231-63-0
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1778-1786Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : KA 3492/3-1
Pays : International
Organisme : Ministry of Higher Education (Ministry of Higher Education, Egypt)
ID : Ahmed Kheimar
Pays : International
Organisme : Studienstiftung des Deutschen Volkes (German National Academic Foundation)
ID : Jakob Trimpert
Pays : International
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