siRNA, miRNA and their possible roles in molecular therapy of chronic human hepatitis B virus infection and hepatocellular carcinoma

Abstract

The study aims to investigate the therapeutic and diagnostic potential of small RNA molecules in hepatic diseases. Small interfering RNAs (siRNAs) targeting HBsAg inhibited HBsAg producing on PLC/PRF/5 and 2.2.15 cells by up to 96.3% and virion production in 2.2.15 cells by up to 71.8%. MTS assay showed that cell growth and viability were not affected and cDNA microarray assay observed no significant off-target gene regulation. Our findings indicate that siRNA can be specific in mediating down-regulation of viral gene expression and virion production. miRNA expression profiling using reverse transcription-real-time PCR was carried out in paired HCC tumor and non-tumor samples and showed that of the 157 miRNAs examined, 28 were upregulated while 14 were downregulated. The knock-down studies in cell lines for the upregulated miR-106b-125 cluster showed that the cluster is necessary for cell proliferation and for the anchorage-independent growth, indicating that the miR-106b-125 cluster may have oncogenic properties.