MiR-130a-3p Regulates the Glycolysis via Targeting PDK1 in Hepatocellular Carcinoma

Abstract MiR-130a-3p has been certified to have low expression in several types of tumors. However, the function of miR-130a-3p in glucose metabolism and hepatocellular carcinoma progression is still elusive. Here we report that miR-130a-3p has explicitly low expression in human HCC tissues and cells and is closely related to the patient's tumor size and grade. Overexpression of miR-130a-3p significantly inhibits the glucose metabolism, proliferation and migration of HCC cells in vitro. In order to further study the effects of miR-130a-3p in the glucose metabolism of HCC cells, we found that overexpression of miR-130a-3p significantly inhibited the expression of pyruvate dehydrogenase kinase 1 (PDK1). Consistently, we confirmed that PDK1 is the target gene of miR-130a-3p through dual luciferase reporter gene assays. Cell rescue experiments showed that PDK1 inhibitors reversed the enhancement of cell proliferation, migration and glucose metabolism by miR-130a-3p inhibitor in Hep3B cells. In terms of mechanism, overexpression of miR-130a-3p targeted and inhibited the expression of PDK1, after which pyruvate dehydrogenase (PDH) is activated, thus glycolysis is inhibited, the production of lactic acid and ATP is reduced, and the ability to proliferate and migrate in HCC cells is weakened. In conclusion, our study highlights efforts to target PDK1 and miR-130a-3p as potential therapeutic strategies for the treatment of HCC.