Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 03 2023
08 03 2023
Historique:
received:
05
08
2022
accepted:
27
02
2023
entrez:
7
3
2023
pubmed:
8
3
2023
medline:
10
3
2023
Statut:
epublish
Résumé
Prognosis of children with high-risk hepatoblastoma (HB), the most common pediatric liver cancer, remains poor. In this study, we found ribonucleotide reductase (RNR) subunit M2 (RRM2) was one of the key genes supporting cell proliferation in high-risk HB. While standard chemotherapies could effectively suppress RRM2 in HB cells, they induced a significant upregulation of the other RNR M2 subunit, RRM2B. Computational analysis revealed distinct signaling networks RRM2 and RRM2B were involved in HB patient tumors, with RRM2 supporting cell proliferation and RRM2B participating heavily in stress response pathways. Indeed, RRM2B upregulation in chemotherapy-treated HB cells promoted cell survival and subsequent relapse, during which RRM2B was gradually replaced back by RRM2. Combining an RRM2 inhibitor with chemotherapy showed an effective delaying of HB tumor relapse in vivo. Overall, our study revealed the distinct roles of the two RNR M2 subunits and their dynamic switching during HB cell proliferation and stress response.
Identifiants
pubmed: 36882565
doi: 10.1038/s42003-023-04630-7
pii: 10.1038/s42003-023-04630-7
pmc: PMC9992519
doi:
Substances chimiques
ribonucleotide reductase M2
EC 1.17.4.-
RRM2B protein, human
EC 1.17.4.-
Ribonucleoside Diphosphate Reductase
EC 1.17.4.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
249Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM134382
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA256464
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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