Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness.
Cancer Sci
; 113(5): 1601-1612, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-35253323
ABSTRACT
Sorafenib is a multikinase inhibitor for the standard treatment of advanced liver cancer patients. However, acquired resistance to sorafenib is responsible for a poor prognosis. Therefore, uncovering the molecular mechanisms underlying sorafenib sensitization can provide biomarkers for sorafenib treatment and improve sorafenib activity in a precise medication. Here, we report that epigenetic suppression of Dicer by the HOXB-AS3/EZH2 complex is responsible for sorafenib resistance. We observed that Dicer expression is inversely correlated with EZH2 levels, HOXB-AS3 expression, sorafenib resistance, and cancer stem cell properties in liver cancer patients. Furthermore, ectopic expression of Dicer induced liver cancer cells resensitization to sorafenib. Mechanistically, we found HOXB-AS3 physically interacts with EZH2 and recruits EZH2 to the Dicer promoter, resulting in epigenetic suppression of Dicer expression. These findings reveal that HOXB-AS3/EZH2 complex-mediated Dicer suppression plays an important role in sorafenib resistance and cancer stemness and provide potential therapeutic strategies for diagnosing and treating liver cancer patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Ribonuclease III
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RNA Helicases DEAD-box
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RNA Longo não Codificante
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article