Over-expression of ADAR1 in mice does not initiate or accelerate cancer formation in vivo .

Autor:	Mendez Ruiz S; St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.; Department of Medicine, Eastern Hill Precinct, Melbourne Medical School, University of Melbourne, Fitzroy, Victoria 3065, Australia., Chalk AM; St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.; Department of Medicine, Eastern Hill Precinct, Melbourne Medical School, University of Melbourne, Fitzroy, Victoria 3065, Australia., Goradia A; St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia., Heraud-Farlow J; St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.; Department of Medicine, Eastern Hill Precinct, Melbourne Medical School, University of Melbourne, Fitzroy, Victoria 3065, Australia., Walkley CR; St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.; Department of Medicine, Eastern Hill Precinct, Melbourne Medical School, University of Melbourne, Fitzroy, Victoria 3065, Australia.
Jazyk:	angličtina
Zdroj:	NAR cancer [NAR Cancer] 2023 Jun 01; Vol. 5 (2), pp. zcad023. Date of Electronic Publication: 2023 Jun 01 (Print Publication: 2023).
DOI:	10.1093/narcan/zcad023
Abstrakt:	Adenosine to inosine editing (A-to-I) in regions of double stranded RNA (dsRNA) is mediated by adenosine deaminase acting on RNA 1 (ADAR1) or ADAR2. ADAR1 and A-to-I editing levels are increased in many human cancers. Inhibition of ADAR1 has emerged as a high priority oncology target, however, whether ADAR1 overexpression enables cancer initiation or progression has not been directly tested. We established a series of in vivo models to allow overexpression of full-length ADAR1, or its individual isoforms, to test if increased ADAR1 expression was oncogenic. Widespread over-expression of ADAR1 or the p110 or p150 isoforms individually as sole lesions was well tolerated and did not result in cancer initiation. Therefore, ADAR1 overexpression alone is not sufficient to initiate cancer. We demonstrate that endogenous ADAR1 and A-to-I editing increased upon immortalization in murine cells, consistent with the observations from human cancers. We tested if ADAR1 over-expression could co-operate with cancer initiated by loss of tumour suppressors using a model of osteosarcoma. We did not see a disease potentiating or modifying effect of overexpressing ADAR1 or its isoforms in the models assessed. We conclude that increased ADAR1 expression and A-to-I editing in cancers is most likely a consequence of tumor formation. (© The Author(s) 2023. Published by Oxford University Press on behalf of NAR Cancer.)
Databáze:	MEDLINE
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