dc.contributor.author | Kong, Xiang Yi | |
dc.contributor.author | Vik, Erik Sebastian | |
dc.contributor.author | Nawaz, Meh Sameen | |
dc.contributor.author | Berges, Natalia | |
dc.contributor.author | Dahl, Tuva Børresdatter | |
dc.contributor.author | Vågbø, Cathrine | |
dc.contributor.author | Suganthan, Rajikala | |
dc.contributor.author | Segers, Filip | |
dc.contributor.author | Holm, Sverre | |
dc.contributor.author | Quiles-Jimenez, Ana | |
dc.contributor.author | Gregersen, Ida | |
dc.contributor.author | Fladeby, Cathrine | |
dc.contributor.author | Aukrust, Pål | |
dc.contributor.author | Bjørås, Magnar | |
dc.contributor.author | Klungland, Arne | |
dc.contributor.author | Halvorsen, Bente | |
dc.contributor.author | Alseth, Ingrun | |
dc.date.accessioned | 2020-11-03T13:14:07Z | |
dc.date.accessioned | 2021-02-10T11:47:08Z | |
dc.date.available | 2020-11-03T13:14:07Z | |
dc.date.available | 2021-02-10T11:47:08Z | |
dc.date.issued | 2020-02-21 | |
dc.identifier.citation | Kong XY, Vik SV, Nawaz MS, Berges N, Dahl TB, Vågbø CB, Suganthan R, Segers F, Holm S, Quiles-Jimenez, Gregersen I, Fladeby C, Aukrust P, Bjørås M, Klungland A, Halvorsen BE, Alseth I. Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma. Nucleic Acids Research. 2020 | en |
dc.identifier.issn | 0305-1048 | |
dc.identifier.issn | 1362-4962 | |
dc.identifier.uri | https://hdl.handle.net/10642/9499 | |
dc.description.abstract | Endonuclease V (EndoV) is a conserved inosinespecific ribonuclease with unknown biological function. Here, we present the first mouse model lacking
EndoV, which is viable without visible abnormalities.
We show that endogenous murine EndoV cleaves
inosine-containing RNA in vitro, nevertheless a series of experiments fails to link an in vivo function to
processing of such transcripts. As inosine levels and
adenosine-to-inosine editing often are dysregulated
in hepatocellular carcinoma (HCC), we chemically induced HCC in mice. All mice developed liver cancer,
however, EndoV−/− tumors were significantly fewer
and smaller than wild type tumors. Opposed to human HCC, adenosine deaminase mRNA expression
and site-specific editing were unaltered in our model.
Loss of EndoV did not affect editing levels in liver
tumors, however mRNA expression of a selection of
cancer related genes were reduced. Inosines are also
found in certain tRNAs and tRNAs are cleaved during
stress to produce signaling entities. tRNA fragmentation was dysregulated in EndoV−/− livers and apparently, inosine-independent. We speculate that the
inosine-ribonuclease activity of EndoV is disabled in
vivo, but RNA binding allowed to promote stabilization of transcripts or recruitment of proteins to finetune gene expression. The EndoV−/− tumor suppressive phenotype calls for related studies in human
HCC. | en |
dc.description.sponsorship | Funding provided by Norwegian Cancer Society [5739724]; Norwegian Research Council [250474, 144245]; Health Authority South East
[2017088, 2018084, 2018064]. Funding for open access charge: Norwegian Research Council [250474]. | en |
dc.language.iso | en | en |
dc.publisher | Oxford University Press | en |
dc.relation.ispartofseries | Nucleic Acids Research;Volume 48, Issue 8 | |
dc.rights | Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.subject | Inosine-specific ribonucleases | en |
dc.subject | Hepatocellular carcinoma | en |
dc.subject | Ribonucleic acids | en |
dc.subject | Cancer | en |
dc.subject | Inosines | en |
dc.title | Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma | en |
dc.type | Journal article | |
dc.type | Peer reviewed | en |
dc.date.updated | 2020-11-03T13:14:07Z | |
dc.description.version | publishedVersion | en |
dc.identifier.doi | https://doi.org/10.1093/nar/gkaa115 | |
dc.identifier.cristin | 1842594 | |
dc.source.journal | Nucleic Acids Research | |