MiR-182 promotes glucose metabolism by upregulating hypoxia-inducible factor 1α in NSCLC cells

This study aims to demonstrate the role of miR-182 in the glucose metabolism of NSCLC cells and the potential mechanism.

MTT Cytotoxicity Assay was used to measure the function of differentially expressed miR-182 on two NSCLC cell lines proliferation. Metabolite analysis was introduced to monitor the glucose consumption, lactate release and glycolytic intermediate metabolites. The mRNA level of critical genes involved in glycolysis was detected by qRT-PCR. The 3'UTRs of predicted gene with a miR-182 binding site and their seed-sequence-mutated version were cloned downstream to the ORF of a Renilla luciferase reporter gene and the ability of miR-182 to downregulate luciferase expression was assessed.

MiR-182 had significantly improved proliferation of NSCLC cell lines. Metabolite analysis of the cells with strengthened miR-182 revealed significantly increased glucose consumption and lactate release, as well as glycolytic intermediate metabolites, or conversely. Among a panel of genes controlling glucose metabolism, miR-182 exhibited significantly influence on ENO1, GLUT1, HIF-1α, HK1, HK2, LDHA and PDK1, especially HIF-1α. For the predicted target gene HIF1AN, the wild-type but not mutated 3'UTR, responded to miR-182  b y directing ∼45% reduction of reporter gene expression.

MiR-182 promotes glucose metabolism by upregulating HIF-1α in NSCLC cells.