In accordance with the data presented in this study, it is shown that Bcl-2 is a direct target of miR-181a, via an independent binding site in its 3′-UTR, which reduces its expression, activity and downstream signaling, and our functional experiments validate Bcl-2 as a critical mediator of the pro-apoptotic effects of miR-181a in melanoma cells. The gene discussed is BCL2; the disease is melanoma.