Taking the above into consideration, several potential mechanisms of action of metformin in HCC have been proposed based on preclinical and clinical studies [42], including the activation of AMPK [43]; the inhibition of mitochondrial complex I, which disrupts cellular energy metabolism, impairing cancer cell growth and survival [44]; the modulation of insulin signaling, which indirectly influences cancer development and progression [45]; the reduction of inflammation [43] and the effects on cancer stem cells (CSCs) [46]. The gene discussed is INS; the disease is cancer.