The upregulation of the cell cycle inhibitor, CDKN1C/p57, is one of the mechanisms underlying the anti-tumor activity of antagomiR-221 in the TG model and, intriguingly, it is a Notch3 target molecule [87], further highlighting the inter-relationships between Notch and HCC-specific miRNAs and providing the rationale for an miRNA-based approach in HCC to complement other Notch-targeted strategies. The gene discussed is NOTCH3; the disease is hepatocellular carcinoma.