例如:"lncRNA", "apoptosis", "WRKY"

Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.

Cancer Cell. 2014 Dec 08;26(6):826-839. Epub 2014 Nov 20
Krishna S Tummala 1 , Ana L Gomes 1 , Mahmut Yilmaz 1 , Osvaldo Graña 2 , Latifa Bakiri 3 , Isabel Ruppen 4 , Pilar Ximénez-Embún 4 , Vinayata Sheshappanavar 5 , Manuel Rodriguez-Justo 6 , David G Pisano 2 , Erwin F Wagner 3 , Nabil Djouder 7
Krishna S Tummala 1 , Ana L Gomes 1 , Mahmut Yilmaz 1 , Osvaldo Graña 2 , Latifa Bakiri 3 , Isabel Ruppen 4 , Pilar Ximénez-Embún 4 , Vinayata Sheshappanavar 5 , Manuel Rodriguez-Justo 6 , David G Pisano 2 , Erwin F Wagner 3 , Nabil Djouder 7
+ et al

[No authors listed]

Author information
  • 1 Growth Factors, Nutrients and Cancer Group, BBVA Foundation-Cancer Cell Biology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain.
  • 2 Bioinformatics Unit, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain.
  • 3 Genes, Development, and Disease Group, BBVA Foundation-Cancer Cell Biology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain.
  • 4 Proteomics Core Unit, ProteoRed ISCIII, Biotechnology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain.
  • 5 Department of Pathology, Royal London Hospital, London E1 1BB, UK.
  • 6 Department of Cellular Pathology, University College London NHS Trust, London NW1 2BU, UK.
  • 7 Growth Factors, Nutrients and Cancer Group, BBVA Foundation-Cancer Cell Biology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain. Electronic address: ndjouder@cnio.es.

摘要


Molecular mechanisms responsible for hepatocellular carcinoma (HCC) remain largely unknown. Using genetically engineered mouse models, we show that hepatocyte-specific expression of unconventional prefoldin RPB5 interactor (URI) leads to a multistep process of HCC development, whereas its genetic reduction in hepatocytes protects against diethylnitrosamine (DEN)-induced HCC. URI inhibits aryl hydrocarbon (AhR)- and estrogen receptor (ER)-mediated transcription of enzymes implicated in L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism, thereby causing DNA damage at early stages of tumorigenesis. Restoring NAD(+) pools with nicotinamide riboside (NR) prevents DNA damage and tumor formation. Consistently, URI expression in human HCC is associated with poor survival and correlates negatively with L-tryptophan catabolism pathway. Our results suggest that boosting NAD(+) can be prophylactic or therapeutic in HCC.

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
duration of huri expressionectopic expressionsource namestrain/backgroundtissue
8 weeks Unconventional prefoldin RPB5 interactor overexpression, replicate 3
Mus musculus GSM1182954: 8 weeks URI overexpression, replicate 3; Mus musculus; RNA-Seq RNA-Seq Illumina Genome Analyzer IIx 8 weeks hURI Liver, hURI expression, 8 weeks C57BL/6 liver (bottom half of right lobe)
8 weeks Unconventional prefoldin RPB5 interactor overexpression, replicate 2
Mus musculus GSM1182953: 8 weeks URI overexpression, replicate 2; Mus musculus; RNA-Seq RNA-Seq Illumina Genome Analyzer IIx 8 weeks hURI Liver, hURI expression, 8 weeks C57BL/6 liver (bottom half of right lobe)
8 weeks Unconventional prefoldin RPB5 interactor overexpression, replicate 1
Mus musculus GSM1182952: 8 weeks URI overexpression, replicate 1; Mus musculus; RNA-Seq RNA-Seq Illumina Genome Analyzer IIx 8 weeks hURI Liver, hURI expression, 8 weeks C57BL/6 liver (bottom half of right lobe)
8 weeks control, replicate 4
Mus musculus GSM1182951: 8 weeks control, replicate 4; Mus musculus; RNA-Seq RNA-Seq Illumina Genome Analyzer IIx 8 weeks none Liver, control, 8 weeks C57BL/6 liver (bottom half of right lobe)
8 weeks control, replicate 3
Mus musculus GSM1182950: 8 weeks control, replicate 3; Mus musculus; RNA-Seq RNA-Seq Illumina Genome Analyzer IIx 8 weeks none Liver, control, 8 weeks C57BL/6 liver (bottom half of right lobe)