A later study found that UPS21 overexpression activated ERK signaling through deubiquitylation and stabilization of MEK2, whose expression partially rescued decreased p-ERK1/2 levels, impaired cell proliferation and anchorage-independent growth, and cell cycle arrest due to USP21 knockdown in HCC cell lines (Li et al., 2018). This evidence concerns the gene MAP2K2 and hepatocellular carcinoma.