Human miR-5193 Triggers Gene Silencing in Multiple Genotypes of Hepatitis B Virus
2015
Hepatitis B virus (HBV) infection can lead to various disease states including asymptomatic,
acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), which
remain a major health problem worldwide. Previous studies demonstrated that microRNA (miRNAs)
plays an important role in viral replication. This study aimed to predict and evaluate human miRNAs targeting multiple
genotypes of HBV. Candidate human miRNAs were analyzed by data obtained from miRBase and RNAhybrid. Then
miRNAs were selected based on hybridization patterns and minimum free energy (MFE). The silencing effect of miRNA
was evaluated by real-time PCR, the luciferase reporter assay and the ELISA assay. Five human miRNAs including miR-
142-5p, miR-384, miR-500b, miR-4731-5p and miR-5193 were found to target several HBV genotypes. Interestingly,
miR-5193 was found to be the most potent miRNA that could target against all HBV transcripts in almost all HBV genotypes
with a highly stable hybridization pattern (5' canonical with MFE lower than -35 kcal/mol). Moreover, miR-5193
caused significant silencing in luciferase activity (53% reduction), luciferase transcript (60% reduction) and HBV surface
antigen (HBsAg) production (20-40% reduction depending on genotypes). Therefore, miR-5193 might be useful and have
a vital role for inhibition of HBV replication in the future.
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