Silencing each of the UCEs Cps1, Ass1, Asl, or Arg1 (silencing of Otc unsuccessful) in the c-MET/sgAxin1 model, where the UCEs were only modestly affected (Fig. 1, D to F), resulted in elevated ammonia burden, together with reprogramming of amino acid metabolism and pyrimidine synthesis, supporting a causative role of defective UC in promoting HCC (Figs. 4 and 5). This evidence concerns the gene ASL and hepatocellular carcinoma.