CREB is a transcription factor that accelerates HCC progression.[24, 26] CREB could be activated by multiple kinases such as MAPK, Akt, PKA, PKC.[35] In our work, we found CREB phosphorylation on Ser133 is dramatically decreased by MEK1/2 inhibitor PD184352, which suggested that ERK1/2 controls CREB activation to a large extent in HCC, the same as a previous article mentioned.[23] Moreover, NRF1 promotes progression of HCC by activating CREB phosphorylation. The gene discussed is PRRT2; the disease is hepatocellular carcinoma.