TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma.
Mol Oncol
; 13(4): 928-945, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30657254
ABSTRACT
Hepatocellular carcinoma (HCC) is a lethal human malignancy and a leading cause of cancer-related death worldwide. Patients with HCC are often diagnosed at an advanced stage, and the prognosis is usually poor. The multikinase inhibitor sorafenib is the first-line treatment for patients with advanced HCC. However, cases of primary or acquired resistance to sorafenib have gradually increased, leading to a predicament in HCC therapy. Thus, it is critical to investigate the mechanism underlying sorafenib resistance. Transactivation response element RNA-binding protein 2 (TARBP2) is a multifaceted miRNA biogenesis factor that regulates cancer stem cell (CSC) properties. The tumorigenicity and drug resistance of cancer cells are often enhanced due to the acquisition of CSC features. However, the role of TARBP2 in sorafenib resistance in HCC remains unknown. Our results demonstrate that TARBP2 is significantly downregulated in sorafenib-resistant HCC cells. The TARBP2 protein was destabilized through autophagic-lysosomal proteolysis, thereby stabilizing the expression of the CSC marker protein Nanog, which facilitates sorafenib resistance in HCC cells. In summary, here we reveal a novel miRNA-independent role of TARBP2 in regulating sorafenib resistance in HCC cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al ARN
/
Carcinoma Hepatocelular
/
Resistencia a Antineoplásicos
/
Proteína Homeótica Nanog
/
Sorafenib
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Taiwán