Kurzfassung

Sirt6, a NAD-dependent deacetylase of the sirtuin gene family is highly expressed in hepatocytes. Its ablation in mice causes a severe aging-like phenotype with impaired liver function and premature death. We investigated Sirt6 expression in over 200 primary human liver cancers, normal and cirrhotic livers using gene array data and further analyzed gene expression signatures, we generated from isolated hepatocytes of Sirt6-deficient mice in this data set. We could show that the...Sirt6, a NAD-dependent deacetylase of the sirtuin gene family is highly expressed in hepatocytes. Its ablation in mice causes a severe aging-like phenotype with impaired liver function and premature death. We investigated Sirt6 expression in over 200 primary human liver cancers, normal and cirrhotic livers using gene array data and further analyzed gene expression signatures, we generated from isolated hepatocytes of Sirt6-deficient mice in this data set. We could show that the Sirt6-deficient hepatocyte signature is prognostically relevant for the patients in relation to survival and tumor recurrence rates. Among the relevant signature genes we identified genes involved in differentiation, that also play a role during liver fibrosis and tumor development. Using disease relevant differentiation models we analyze the molecular role of Sirt6 in gene regulatory networks in fibrosis and liver cancer.
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