MicroRNA (miRNA) is an endogenous, small, single-strand, noncording RNA consisting of 20 to 25 bases and regulates gene expression of various cell types. It plays an important role in various biological processes, including organ development and differentiation as well as cellular death and proliferation, and is also involved in various diseases such as infection and cancer.1–3
miRNAs are produced as follows. A primary miRNA with a hairpin loop structure is cleaved into a precursor miRNA and transported out of the nuclei with a carrier protein (Exportin-5). The precursor miRNA is then processed by Dicer and converted into an active single-strand RNA in the cytoplasm. The miRNA binds to a target messenger RNA in a sequence-dependent manner and induces degradation of the target messenger RNA and translational inhibition. One miRNA regulates the expression of multiple target genes; bioinformatics analyses have suggested that the expression of more than 30% of human genes is regulated by miRNAs.4–7
Infection of the human liver with hepatitis B virus (HBV) and hepatitis C virus (HCV) induces the development of chronic hepatitis (CH), cirrhosis, and in some instances hepatocellular carcinoma (HCC).8 The virological features of these two distinct viruses are completely different; however, the viruses infect the liver and cause CH, which is not distinguished by histological examination or clinical manifestations. We previously reported that gene expression profiles in chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. Proapoptotic and DNA repair responses were predominant in CH-B, and inflammatory and antiapoptotic phenotypes were predominant in CH-C. However, factors inducing these differences in gene expression remain to be elucidated.9, 10
We examined miRNA expression in liver tissue with HBV-related liver disease (CH-B and HCC-B) and HCV-related liver disease (CH-C and HCC-C) and in normal liver tissue via real-time detection polymerase chain reaction (RTD-PCR). We also performed global analysis of messenger RNA expression in these tissues using complementary DNA (cDNA) microarray. These analyses allowed us to find characteristic miRNAs associated with HBV or HCV infection as well as the progression of liver disease.