Further mechanism studies showed that RPS3 knockdown in melanoma cells triggered the release of cytochrome C (Cyto C) from mitochondrial, increased the location of BID on mitochondrial membrane and the cleavage of the pro-apoptotic proteins (PARP, caspase-3 and -9), promoted the opening of mitochondrial permeability transition pore and the flooding of calcium ions (Ca2+) into the mitochondrial, and decreased the expression of the Ca2+ gatekeeper MICU1 and its location on the mitochondrial. Here, CASP3 is linked to melanoma.