Down-regulation of miR-214 inhibits proliferation and glycolysis in non-small-cell lung cancer cells via down-regulating the expression of hexokinase 2 and pyruvate kinase isozyme M2

Glycolysis is a metabolic pathway that is enhanced in cancer cells. miR-214 plays an important role in cancer development and can modulate glycolysis. However, whether miR-214 can regulate glycolysis in non-small-cell lung cancer (NSCLC) cells has not yet been investigated. The expression levels of miR-214 in 7 NSCLC cell lines were measured by qRT-PCR. MTT assay was performed to evaluate the cell proliferation. Glucose consumption and lactate production were measured to assess the level of glycolysis. The expression of hexokinase 2 (HK2) and pyruvate kinase isozyme M2 (PKM2) was measured by qRT-PCR and western blot analysis. Luciferase reporter assay was carried out to confirm the target gene of miR-214. The levels of PTEN, p-Akt, Akt, p-mTOR, mTOR, p-S6K, and S6K were assessed by western blot analysis. Results showed that miR-214 levels were significantly increased in the 7 NSCLC cell lines compared with those in the human bronchial epithelial cell line. Down-regulation of miR-214 inhibited cell proliferation, glucose consumption, lactate production, and expression of HK2 and PKM2 in NSCLC cells. We also confirmed that miR-214 directly targeted PTEN and regulated the PTEN/Akt/mTOR pathway. Inhibition of the PTEN/Akt/mTOR pathway attenuated the effect of miR-214 mimics on glucose consumption, lactate production, and expression of HK2 and PKM2 in NSCLC cells. These results demonstrated that miR-214 down-regulation inhibited cell proliferation and glycolysis by down-regulating the expression of HK2 and PKM2 via the PTEN/Akt/mTOR pathway in NSCLC cells. Hence, our findings suggested that miR-214 might serve as a novel therapeutic target for NSCLC.