SMAD3 and hepatocellular carcinoma: Subsequently, xenograft models of HCC involving male BALB/c nude mice and humanized hepatoma cell lines (HepG2 cells) were used to investigate how microRNA-21 antagomir and microRNA-145 agomir mediate tumor progression and apoptosis and the underlying mechanisms involving domain-specific Smad3 phosphorylation mediated by TGF-β and MAPK signaling.