In HepG2 cells and primary HCC cells (derived from two other HCC patients, HCC-2/HCC-3), HBO1 silencing by HBO1-shRNA-2 (see Fig. 2) increased caspase-3 activity (Fig. 3G) and induced mitochondrial depolarization (JC-1 green monomers intensity increase, Fig. 3H). Here, CASP3 is linked to hepatocellular carcinoma.