Functionally, APPLE promotes Extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, activates The Mitogen-Activated Protein Kinase (MAPK) signaling, and enhances HCC cell proliferation, migration, invasion, and tumor growth effects, which are reversed by APPLE knockdown or ERK1/2 inhibition [32]. This evidence concerns the gene MAPK3 and neoplasm.