Academic Journal
Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma
| العنوان: | Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma |
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| المؤلفون: | Kong, 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 |
| المصدر: | 0305-1048. |
| سنة النشر: | 2020 |
| المجموعة: | Universitet i Oslo: Digitale utgivelser ved UiO (DUO) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | http://urn.nb.no/URN:NBN:no-83972; Kong, 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; http://hdl.handle.net/10852/80881; 1842594; info: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; Nucleic Acids Research; 48; 4463; 4479; https://doi.org/10.1093/nar/gkaa115; URN:NBN:no-83972; Fulltext https://www.duo.uio.no/bitstream/handle/10852/80881/1/gkaa115.pdf |
| DOI: | 10.1093/nar/gkaa115 |
| الاتاحة: | http://hdl.handle.net/10852/80881 http://urn.nb.no/URN:NBN:no-83972 https://doi.org/10.1093/nar/gkaa115 |
| Rights: | Attribution-NonCommercial 4.0 International ; https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.5C0972C1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/nar/gkaa115 |
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