Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models.

ABSTRACT

Emerging evidence has suggested that aberrant expression of micro (mi)RNAs contributes to the development of alcoholic liver injury (ALD). However, miRNA profiles distinguishing different stages of ALD have not yet been reported. The present study was designed to investigate the unique miRNA expression patterns at different stages of ALD in a rat model and analyze the gene functions and pathways of dysregulated miRNA­targeted genes. Using microarray and stem­loop quantitative polymerase chain reaction analyses, 16 miRNAs were identified as upregulated and 13 were identified as downregulated in an alcoholic steatohepatitis (ASH) group compared with the control group, while five miRNAs were identified to be upregulated and eight were identified to be downregulated in the alcoholic fatty liver (AFL) group as compared with the control group. Following further confirmation by Significance Analysis of Microarray and prediction by Prediction Analysis of Microarray, 8 and 12 types of miRNA were screened as molecular signatures in distinguishing AFL and ASH, respectively, from normal rat liver. In addition, several miRNA­target pairs were predicted by computer­aided algorithms (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery platform) and these genes may be involved in cancer signaling pathways, the Wnt signaling pathway and other signaling pathways. These results may provide novel miRNA targets for diagnosis and therapeutic intervention at different stages of ALD.