3) Ectopically expressed RNF2 results in a decrease in SIK1 levels in HCC cell lines by accelerating its degradation; 4) RNF2 physically interacts with SIK1 and is an E3 ligase of SIK1, suggesting that RNF2 is an important upstream negative regulator of SIk1 in HCC. The gene discussed is RNF2; the disease is hepatocellular carcinoma.