Gene expression analysis of micoRNA-221 overexpressing transgenic mice livers with and without metformin intervention upon chronic liver injury induced by carbon tetrachloride

Metformin is a hypoglycaemic agent used to treat type 2 diabetes mellitus (DM2) patients, with a broad safety profile. Since previous epidemiological studies had shown that incidence of hepatocellular carcinoma (HCC) decreased significantly in metformin treated DM2 patients, we hypothesized that intervention with metformin could reduce the risk of neoplastic transformation of hepatocytes. HCC is the most common primary liver malignancy and it generally originates in a background of liver fibrosis and cirrhosis. In the present study, we took advantage of a transgenic mouse (TG221) characterized by microRNA-221 overexpression, with cirrhotic liver background induced by chronic administration of carbon tetrachloride (CCl4). This mouse model develops fibrosis, cirrhosis and liver tumors that become visible in 100% of mice at 5-6 months of age. We compared geneset enrichment of differentially expressed genes in livers between metformin+CCl4 and CCl4 treated TG221 mice. Chronic liver injury was induced in all mice with CCl4 for 14 weeks and metformin intervention was started after 3 weeks of initiating CCl4 challenge until the experimental end-point of 24 weeks.