MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation

Deregulation of microRNAs in human malignancies has been well documented, among which microRNA-186 (miR-186) has an antiproliferative role in some carcinomas. Here we demonstrate that low expression of miR-186 facilitates aerobic glycolysis in gastric cancer. MiR-186 suppresses cell proliferation induced by hypoxia inducible factor 1 alpha (HIF-1 alpha) in gastric cancer cell lines MKN45 and SGC7901. Cellular glycolysis, including cellular glucose uptake, lactate, ATP/ADP and NAD+/NADH ratios, are also inhibited by miR-186. The negative regulation of miR-186 on HIF-1 alpha effects its downstream targets, including programmed death ligand 1 and two glycolytic key enzymes, hexokinase 2 and platelet-type phosphofructokinase. The antioncogenic effects of miR-186 are proved by in vivo xenograft tumor experiment. The results demonstrate that the miR-186/HIF-1 alpha axis has an antioncogenic role in gastric cancer.