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Let-7b is a novel regulator of hepatitis C virus replication.
Cheng, Ju-Chien; Yeh, Yung-Ju; Tseng, Ching-Ping; Hsu, Sheng-Da; Chang, Yu-Ling; Sakamoto, Naoya; Huang, Hsien-Da.
Afiliação
  • Cheng JC; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, ROC. jccheng@mail.cmu.edu.tw
Cell Mol Life Sci ; 69(15): 2621-33, 2012 Aug.
Article em En | MEDLINE | ID: mdl-22391672
The non-coding microRNA (miRNA) is involved in the regulation of hepatitis C virus (HCV) infection and offers an alternative target for developing anti-HCV agent. In this study, we aim to identify novel cellular miRNAs that directly target the HCV genome with anti-HCV therapeutic potential. Bioinformatic analyses were performed to unveil liver-abundant miRNAs with predicted target sequences on HCV genome. Various cell-based systems confirmed that let-7b plays a negative role in HCV expression. In particular, let-7b suppressed HCV replicon activity and down-regulated HCV accumulation leading to reduced infectivity of HCVcc. Mutational analysis identified let-7b binding sites at the coding sequences of NS5B and 5'-UTR of HCV genome that were conserved among various HCV genotypes. We further demonstrated that the underlying mechanism for let-7b-mediated suppression of HCV RNA accumulation was not dependent on inhibition of HCV translation. Let-7b and IFNα-2a also elicited a synergistic inhibitory effect on HCV infection. Together, let-7b represents a novel cellular miRNA that targets the HCV genome and elicits anti-HCV activity. This study thereby sheds new insight into understanding the role of host miRNAs in HCV pathogenesis and to developing a potential anti-HCV therapeutic strategy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepacivirus / MicroRNAs Limite: Humans Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepacivirus / MicroRNAs Limite: Humans Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2012 Tipo de documento: Article