ML221, an APJ antagonist, could inhibit Apelin-PI3K/Akt signaling pathway and HCC growth both in vitro and in vivo. In a study by Huang et al., it demonstrated that apelin-13 may induce autophagy in HCC cell line HepG2 cells by activating ERK1/2 and upregulating Beclin1 expression (63). This evidence concerns the gene APLNR and hepatocellular carcinoma.