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dc.date.accessioned2020-11-06T18:55:52Z
dc.date.available2020-11-06T18:55:52Z
dc.date.created2020-10-27T13:06:53Z
dc.date.issued2020
dc.identifier.citationKong, Xiang Yi Vik, Erik Sebastian Nawaz, Meh Sameen Berges, Natalia Dahl, Tuva Børresdatter Vågbø, Cathrine Suganthan, Rajikala Segers, Filip Holm, Sverre Quiles-Jimenez, Ana Gregersen, Ida Fladeby, Cathrine Aukrust, Pål Bjørås, Magnar Klungland, Arne Halvorsen, Bente Alseth, Ingrun . Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma. Nucleic Acids Research. 2020
dc.identifier.urihttp://hdl.handle.net/10852/80881
dc.description.abstractAbstract Endonuclease V (EndoV) is a conserved inosine-specific 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 fine-tune gene expression. The EndoV−/− tumor suppressive phenotype calls for related studies in human HCC.
dc.languageEN
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titleDeletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma
dc.typeJournal article
dc.creator.authorKong, Xiang Yi
dc.creator.authorVik, Erik Sebastian
dc.creator.authorNawaz, Meh Sameen
dc.creator.authorBerges, Natalia
dc.creator.authorDahl, Tuva Børresdatter
dc.creator.authorVågbø, Cathrine
dc.creator.authorSuganthan, Rajikala
dc.creator.authorSegers, Filip
dc.creator.authorHolm, Sverre
dc.creator.authorQuiles-Jimenez, Ana
dc.creator.authorGregersen, Ida
dc.creator.authorFladeby, Cathrine
dc.creator.authorAukrust, Pål
dc.creator.authorBjørås, Magnar
dc.creator.authorKlungland, Arne
dc.creator.authorHalvorsen, Bente
dc.creator.authorAlseth, Ingrun
cristin.unitcode185,53,48,14
cristin.unitnameInstitutt for indremedisinsk forskning
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.cristin1842594
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nucleic Acids Research&rft.volume=&rft.spage=&rft.date=2020
dc.identifier.jtitleNucleic Acids Research
dc.identifier.volume48
dc.identifier.issue8
dc.identifier.startpage4463
dc.identifier.endpage4479
dc.identifier.doihttps://doi.org/10.1093/nar/gkaa115
dc.identifier.urnURN:NBN:no-83972
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn0305-1048
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/80881/1/gkaa115.pdf
dc.type.versionPublishedVersion


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