Aside from AKT signaling, AMPK is greatly involved in regulating ATP generation after energy deprivation, the stressful condition that can be induced by sorafenib treatment.31 Of note, it has been already revealed that SESN2 was responsible for AMPK activation to facilitate autophagy in protecting HCC cells from death.32 Hence, we proposed that SESN2 might mediate AMPK to maintain HCC cell survival after sorafenib treatment. This evidence concerns the gene PRKAA1 and hepatocellular carcinoma.