MAPK1 and hepatocellular carcinoma: As shown in Fig. 6D, we found the mechanism behind this: the loss of NF1 and DUSP9 can activate the PI3K/AKT and MAPK/ERK signaling pathways, thereby inactivating FOXO3, followed by degradation of FOXO3; this results in the progression of HCC, which is inhibited by lenvatinib.