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Overexpression of cellular telomerase RNA enhances virus-induced cancer formation

Oncogene volume 38, pages 1778–1786 (2019)Cite this article

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Abstract

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.

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Acknowledgements

We thank Ann Reum for the technical assistance and Dr. Laura Pieper for her statistical consultation.

Funding:

DFG grant (KA 3492/3–1), Ministry of High Education Egypt (MOHE), and Studienstiftung des deutschen Volkes.

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Authors and Affiliations

  1. Institut für Virologie, Freie Universität Berlin, Robert von Ostertag-Straße 7-13, 14163, Berlin, Germany

    Ahmed Kheimar, Jakob Trimpert, Nicole Groenke & Benedikt B. Kaufer

  2. Department of Poultry Diseases, Faculty of Veterinary Medicine, Sohag University, 82424, Sohag, Egypt

    Ahmed Kheimar

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  1. Ahmed Kheimar
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Correspondence to Benedikt B. Kaufer.

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Kheimar, A., Trimpert, J., Groenke, N. et al. Overexpression of cellular telomerase RNA enhances virus-induced cancer formation. Oncogene 38, 1778–1786 (2019). https://doi.org/10.1038/s41388-018-0544-1

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