Lung alveolar epithelial cells are exposed to
hypoxia under a variety of physiological and pathological conditions. It has been shown recently that miR-143, which can directly target the key glycolytic
enzyme hexokinase II (HK2), may be regulated by miR-155. We investigated whether
microRNAs contribute to the cellular glycolysis in response to
hypoxia. Using the A549 cells, we found that the expression of Dicer is decreased under
hypoxia. When Dicer was knocked down with
small-interfering RNA (
siRNA), pre-miR143 was increased and mature miR-143 was decreased as that in
hypoxia, indicating that reduction of Dicer is responsible for the change of miR-143 under
hypoxia. Interestingly, both
hypoxia and knockdown of Dicer resulted in miR-155 and pre-miR-155 expression increases. We also examined the expression of HK2 and
glucose metabolism in the cells. Both HK2
mRNA and
protein were increased under
hypoxia, which is accompanied by an increase of
glucose uptake and production of
lactate. The same alterations were found with
siRNA Dicer knockdown. Moreover, transfection with anti-miR-143 also led to a HK2 production and an increase of
glucose uptake and
lactate production, whereas anti-miR-155 had opposite effects. The miR-143 and anti-miR-155 transfection resulted in a significant cell apoptosis. The expression of Dicer was decreased with HK2 accumulating in mouse lung tissues under
hypoxia identified by immunohistochemistry. The changes of miR-143 and miR-155 were similar to those in A549 cells. Our data demonstrate that Dicer regulation of
miRNAs promotes HK2 activation and glycolysis, which might protect the cell from hypoxic damage and enter into an adaptive process.