As shown in Fig. 5a, the expression of the phosphorylated Drosophila mothers against decapentaplegic protein 2/3 (p-Smad2/3) was reduced by RNF38 knockdown, but there were no significant changes in the expression of phosphorylated AKT or ERK1/2, indicating that a high level of RNF38 might promote HCC progression mainly via TGF-β1/Smad signaling. This evidence concerns the gene TGFB1 and hepatocellular carcinoma.