1, 2 MiRNAs are engaged in either translational arrest or degradation of targeted transcripts through imperfect base pairing with the 3′-untranslated region (UTR) of the target transcripts. Intriguingly, miRNAs may also lead to an up-regulation of gene expression by targeting 5′UTR3, 4 or under cell cycle arrest conditions.5 Functional messenger RNA (mRNA) targets are generally fully complementary to nucleotides 2-8 at the 5′ end of the miRNA, referred to as the miRNA “seed region.”6 Bioinformatic analyses have suggested that a single miRNA may suppress a number of genes and each mRNA can be targeted by multiple miRNAs.7 It is estimated that more than 30% of human genes are regulated by miRNAs.8 At present,

the roles of cellular miRNAs

in viral life cycles are under investigation. Recent findings highlighted that miRNAs of host cells may affect viral gene expression in direct or indirect manners LDE225 research buy and may play a significant role in maintenance of viral replication, latency, and evasion of the host immune system.9 For example, the human miR-32 inhibits the accumulation of primate foamy virus type 1 in host cells.10 In contrast, miR-122 facilitates hepatitis C virus (HCV) replication by binding to the 5′ end of the viral genome.3 Additionally, interferon beta (IFN-β) was reported to modulate the expression of several cellular Akt inhibitor miRNAs to inhibit HCV replication.11 Hepatitis B virus (HBV) is an enveloped DNA virus of the family Hepadnaviridae and causes acute and chronic hepatitis in humans.12 HBV replication is dependent on host cell proliferation status13

and controlled by a variety of cellular transcription factors, in particular, several nuclear receptors like farnesoid X receptor α (FXRA), hepatocyte nuclear factor 4α (HNF4A), liver X receptor (LXR), retinoid X receptor α (RXRA), and peroxisome proliferator activated receptor α/γ (PPARA/G).14, 15 Recent diglyceride studies have shown that miRNA expression profiles could be affected by HBV infection in HBV-related hepatocellular carcinoma.16 Some miRNA-regulated genes related to immune response, cell death, DNA damage and recombination, and transcription showed a decreased expression pattern, suggesting the involvement of miRNAs in HBV infection and HBV-related carcinogenesis.16 Considering the possibility that cellular miRNAs may play an important role in HBV pathogenesis, a number of miRNAs were selected and their effect on HBV replication was examined in HBV-expressing hepatoma cell lines. Our data suggest that miR-1 is able to regulate the expression of multiple cellular genes, inhibit cell proliferation, and promote cell differentiation, resulting in the enhancement of HBV replication in hepatoma cells. Our results provide a new concept to understand the role of miRNAs in HBV replication and present a useful way to identify host factors involved in HBV life cycle.