CRISPR/Cas9-mediated knockout of HBsAg inhibits proliferation and tumorigenicity of HBV-positive hepatocellular carcinoma cells.
J Cell Biochem
; 119(10): 8419-8431, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29904948
ABSTRACT
Chronic hepatitis B virus (HBV) infection remains the most common risk factor for hepatocellular carcinoma (HCC). High HBV surface antigen (HBsAg) levels are highly correlated with hepatocarcinogenesis and HBV-associated HCC development. However, the role and detailed mechanisms associated with HBsAg in HCC development remain elusive. In this study, we designed specific single guide RNAs (sgRNAs) targeting the open reading frames, preS1/preS2/S, of the HBV genome and established HBsAg knockout HCC cell lines using the CRISPR/Cas9 system. We showed that knockout of HBsAg in HCC cell lines decreased HBsAg expression and significantly attenuated HCC proliferation in vitro, as well as tumorigenicity in vivo. We also found that overexpression of HBsAg, including the large (LHBs), middle (MHBs), and small (SHBs) surface proteins promoted proliferation and tumor formation in HCC cells. Moreover, we demonstrated that knockout of HBsAg in HCC cells decreased interleukin (IL)-6 production and inhibited signal transducer and activator of transcription 3 (STAT3) signaling, while overexpression of HBsAg induced a substantial accumulation of pY-STAT3. Collectively, these results highlighted the tumorigenic role of HBsAg and implied that the IL-6-STAT3 pathway may be implicated in the HBsAg-mediated malignant potential of HBV-associated HCC.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
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Carcinoma Hepatocelular
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Carcinogênese
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Sistemas CRISPR-Cas
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Antígenos de Superfície da Hepatite B
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Neoplasias Hepáticas
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article