Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer.
Cell biology
Metabolomics
Proteomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
15 Apr 2022
15 Apr 2022
Historique:
received:
29
12
2020
revised:
10
11
2021
accepted:
08
03
2022
entrez:
29
3
2022
pubmed:
30
3
2022
medline:
30
3
2022
Statut:
epublish
Résumé
Castration-resistant prostate cancer (CRPC) is incurable and remains a significant worldwide challenge (Oakes and Papa, 2015). Matched untargeted multi-level omic datasets may reveal biological changes driving CRPC, identifying novel biomarkers and/or therapeutic targets. Untargeted RNA sequencing, proteomics, and metabolomics were performed on xenografts derived from three independent sets of hormone naive and matched CRPC human cell line models of local, lymph node, and bone metastasis grown as murine orthografts. Collectively, we tested the feasibility of muti-omics analysis on models of CRPC in revealing pathways of interest for future validation investigation. Untargeted metabolomics revealed NAA and NAAG commonly accumulating in CRPC across three independent models and proteomics showed upregulation of related enzymes, namely N-acetylated alpha-linked acidic dipeptidases (FOLH1/NAALADL2). Based on pathway analysis integrating multiple omic levels, we hypothesize that increased NAA in CRPC may be due to upregulation of NAAG hydrolysis via NAALADLases providing a pool of acetyl Co-A for upregulated sphingolipid metabolism and a pool of glutamate and aspartate for nucleotide synthesis during tumor growth.
Identifiants
pubmed: 35345457
doi: 10.1016/j.isci.2022.104056
pii: S2589-0042(22)00326-1
pmc: PMC8957019
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104056Subventions
Organisme : Medical Research Council
ID : MR/L017997/1
Pays : United Kingdom
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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