Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients

In this study, we compared circulating miRNAs identified in hepatitis C virus (HCV)-infected patients presenting two extremes of liver disease: mild/moderate fibrosis and cirrhosis. The patients in the cirrhosis group subsequently developed hepatocellular carcinoma (HCC). Methods: Expression profile of miRNA were identify by semiconductor sequencing using Ion Proton High Power Sequencer. The sequences were exported in FASTQ format for further analysis using the CLC Genomics Workbench software version 8.5. The transcripts were trimmed and then annotated by comparing sequence similarity to miRBASE. After identification of mature miRNAs, differential expression analysis of miRNAs between the mild fibrosis and cirrhosis groups was performed using Empirical Analysis of Differential Gene Expression (EDGE). To verify the potential target genes regulated by the differentially expressed miRNAs identified between the two groups studied, the miRnet tool version 2.0 was applied to identify the regulatory networks in which the miRNAs are involved. Results: We identified 163 mature miRNAs in the mild/moderate fibrosis group and 171 in the cirrhosis group, with 144 in common to both groups. Differential expression analysis revealed 5 upregulated miRNAs and 2 downregulated miRNAs in the cirrhosis group relative to the mild/moderate fibrosis group. Functional analyses of regulatory networks (target gene and miRNA) identified gene categories involved in cell cycle biological processes and metabolic pathways related to cell cycle, cancer, and apoptosis. Conclusion:These results suggest that the differentially expressed circulating miRNAs observed in this work (miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p and miR -197-3p) may be candidates for biomarkers in the prognosis of liver disease. Overall design: Serum miRNA profiles of chronic hepatitis C patients