MicroRNA20 induces methylation of hepatitis B virus covalently closed circular DNA in human hepatoma cells.
Mol Med Rep
; 20(3): 2285-2293, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-31257511
ABSTRACT
Methylation was suggested to suppress the transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in hepatocytes. This may be associated with its low replicative activity during the inactive stage of chronic HBV infection; however, the exact mechanisms of methylation in HBV infection remain unknown. We have previously shown that short hairpin RNAs induced the methylation of the HBV genome in hepatoma cell lines. We also reported that the microRNA (miR) 1792 cluster negatively regulates HBV replication in human hepatoma cells. In addition, miR20a, a member of the miR 1792 cluster, has sequence homology with the short hairpin RNA that induces HBV methylation. In the present study, we investigated whether miR20a can function as an endogenous effector of HBV DNA methylation. The results indicated that overexpression of miR20a could suppress the replicative activity of HBV and increased the degree of methylation of HBV cccDNA in the HepAD38 hepatoma cell line. Argonaute (AGO)1 and AGO2, effectors of the RNAinduced silencing complex, were detected in the nucleus of HepAD38 cells; however, only AGO2 was bound to HBV cccDNA. In addition, intranuclear AGO2 was determined to be bound with miR20a. In conclusion, miR20a may be loaded onto AGO2, prior to its translocation into the nucleus, inducing the methylation of HBV DNA in human hepatoma cells, leading to the suppression of HBV replication.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN Viral
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Virus de la Hepatitis B
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Carcinoma Hepatocelular
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Metilación de ADN
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MicroARNs
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article