Long noncoding RNA PVT1 inhibits interferon-α mediated therapy for hepatocellular carcinoma cells by interacting with signal transducer and activator of transcription 1.
Biochem Biophys Res Commun
; 500(4): 973-980, 2018 06 12.
Article
en En
| MEDLINE
| ID: mdl-29715456
Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC) and hsigh expression of oncogenic PVT1 is associated with poor prognosis of HCC. Interferon-α (IFN-α) has been used in clinic for HCC therapy. However, whether PVT1 is involved in the IFN-α therapy for HCC is completely unknown. Our study found that high PVT1 expression in HCC cells is associated with high unmethylation in PVT1 promoter region. IFN-α treatment further increases PVT1 expression in HCC cells by enhancing H3K4me3 modification on the promoter. Furthermore, PVT1 knockdown enhances IFN-α-induced HCC cell apoptosis by promoting phosphorylation of signal transducer and activator of transcription 1 (STAT1) and upregulating IFN-stimulated genes expression. Moreover, PVT1 specifically interacts with STAT1 in HCC cells. Taken together, these results for the first time indicate that IFN-α treatment promotes oncogenic PVT1 expression in HCC cells, which interacts with STAT1 to inhibit IFN-α signaling, ultimately blocking IFN-α-induced cells apoptosis, suggesting that lncRNA PVT1 may be a potential target to improve IFN-α-mediated HCC immunotherapies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histonas
/
Regulación Neoplásica de la Expresión Génica
/
Interferón-alfa
/
Factor de Transcripción STAT1
/
ARN Largo no Codificante
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos