Hypoxia-induced miR-214 expression promotes tumour cell proliferation and migration by enhancing the Warburg effect in gastric carcinoma cells

Abstract

miR-214 is an important oncomiRNA and is upregulated in various types of cancer, including gastric cancer. However, the molecular mechanism underlying the ectopic expression and function of miR-214 in gastric cancer is largely undefined. In this study, we found that miR-214 induces the Warburg effect and promotes the migration and proliferation of human gastric cancer cells. According to the mechanistic analysis, miR-214 expression is induced by environmental hypoxia, and miR-214 mediates hypoxia-induced functions. We then explored the molecular mechanism by which miR-214 enhances the Warburg effect in gastric cancer cells and identified the adenosine A2A receptor (A2AR) and PR/SET domain 16 (PRDM16) genes as the direct targets of miR-214. In conclusion, miR-214 inhibits A2AR and PRDM16 expression and enhances the Warburg effect in gastric cancer cells, thus promoting the proliferation and migration of gastric cancer cells. This study highlights an important role for the hypoxia-miR-214-PRDM16/A2AR pathway in the tumourigenesis of gastric cancer and may facilitate the development of new therapeutics against hypoxic tumours.