ATXN7L3B promotes hepatocellular carcinoma stemness and is downregulated by metformin.
Biochem Biophys Res Commun
; 573: 1-8, 2021 10 08.
Article
en En
| MEDLINE
| ID: mdl-34375763
ABSTRACT
Hepatocellular carcinoma (HCC) is the major cause of liver cancer-associated morality. Metformin, used for treating type 2 diabetes, has antitumor activity and reduces the risk of some diabetes-related tumors, such as liver and breast cancer. However, the mechanisms underlying metformin's effects in HCC remain unclear. To identify genes associated with metformin treatment in HCC, we conducted transcriptomic and proteomic analyses in HCC cells treated with or without metformin. We identified 41 differentially expressed genes upon metformin treatment. Among them, Ataxin 7 Like 3B (ATXN7L3B), which is a negative regulator of the Spt-Ada-Gcn5 acetyltransferase (SAGA) deubiquitinase (DUB) module and has relatively unknown functions in cancer, attracted our attention. We observed that metformin reduced ATXN7L3B level in HCC cells. ATXN7L3B expression was significantly negatively correlated with survival in liver cancer patients. We also demonstrated that ATXN7L3B promoted HCC stemness. Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B. Our study supports the antitumor activity of metformin and its potential as an anticancer drug for HCC treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
China