SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.
Cancer
Drugs
Epigenetics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 Jul 2023
21 Jul 2023
Historique:
received:
24
11
2022
revised:
19
03
2023
accepted:
25
05
2023
medline:
3
8
2023
pubmed:
3
8
2023
entrez:
3
8
2023
Statut:
epublish
Résumé
Drug resistance prominently hampers the effects of systemic therapy of sorafenib to hepatocellular carcinoma (HCC). Epigenetics have critical regulatory roles in drug resistance. However, the contributions of histone methylatransferase SET and MYND domain containing 3 (SMYD3) to sorafenib resistance in HCC remain largely unknown. Here, using our established sorafenib-resistant HCC cell and xenograft models, we found SMYD3 was markedly elevated in sorafenib-resistant tumors and cells. Functionally, loss- and gain-of-function studies showed that SMYD3 promoted the migration, invasion, metastasis and stemness of sorafenib-resistant HCC cells. Mechanistically, SMYD3 is required for SMAD2/3-mediated epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by interacting with SMAD2/3 and epigenetically promoting the expression of
Identifiants
pubmed: 37534166
doi: 10.1016/j.isci.2023.106994
pii: S2589-0042(23)01071-4
pmc: PMC10391607
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106994Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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