Changes in micro RNA expression during disease progression in patients with chronic viral hepatitis.

Background & Aims Micro RNAs (mi RNAs) have been involved in hepatocarcinogenesis, but little is known on their role in the progression of chronic viral hepatitis. Aim of this study was to identify mi RNA signatures associated with stages of disease progression in patients with chronic viral hepatitis. Methods Mi RNA expression profile was investigated in liver biopsies from patients with chronic viral hepatitis and correlated with clinical, virological and histopathological features. Relevant mi RNAs were further investigated. Results Most of the significant changes in mi RNA expression were associated with liver fibrosis stages and included the significant up-regulation of a group of mi RNAs that were demonstrated to target the master regulators of epithelial-mesenchymal transition ZEB1 and ZEB2 and involved in the preservation of epithelial cell differentiation, but also in cell proliferation and fibrogenesis. In agreement with mi RNA data, immunostaining of liver biopsies showed that expression of the epithelial marker E-cadherin was maintained in severe fibrosis/cirrhosis while expression of ZEBs and other markers of epithelial-mesenchymal transition were low or absent. Severe liver fibrosis was also significantly associated with the down-regulation of mi RNAs with antiproliferative and tumour suppressor activity. Similar changes in mi RNA and target gene expression were demonstrated along with disease progression in a mouse model of carbon tetrachloride ( CCl4)-induced liver fibrosis, suggesting that they might represent a general response to liver injury. Conclusion Chronic viral hepatitis progression is associated with the activation of mi RNA pathways that promote cell proliferation and fibrogenesis, but preserve the differentiated hepatocyte phenotype. [ABSTRACT FROM AUTHOR]