Beta-Elemene Suppresses Warburg Effect In Nci-H1650 Non-Small-Cell Lung Cancer Cells By Regulating The Mir-301a-3p/Ampk Alpha Axis

BIOSCIENCE REPORTS(2020)

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摘要
beta-elemene has been evidenced to suppress the development of numerous cancers including lung cancer. Previous research has found that in A549 cells, beta-elemene increased the expression of adenosine monophosphate-activated protein kinase (AMPK) alpha (AMPKa), which negatively regulates the Warburg effect. Bioinformatics predicted that binding sites exist between AMPK alpha and miR-301a-3p, an miRNA that has shown oncogenic function in many cancers. The aim of this work was to investigate the effect of beta-elemene on the Warburg effect in non-small-cell lung cancer (NSCLC) cells and its mechanism. Herein, the expression of miR-301a-3p was evaluated in NSCLC cells. Then, miR-301a-3p was overexpressed or silenced by mimics or inhibitors, respectively, followed by treatment with AMPK agonists or antagonists. NSCLC cells subjected to miR-301a-3p overexpression or inhibition were further treated with beta-elemene. The results demonstrated that AMPKa was targeted and negatively regulated by miR-301a-3p. AMPKa agonists attenuated the Warburg effect in NSCLC cells induced by miR-301a-3p, as evidenced by the decrease in glucose level, lactic acid level, and expression of metabolism-related enzymes (glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA)). Additionally, beta-elemene suppressed the expression of miR-301a-3p, enhanced that of AMPKa, and inhibited the Warburg effect in NSCLC cells. The results indicated that beta-elemene attenuates the Warburg effect in NSCLC cells, possibly by mediating the miR-301a-3p/AMPKa axis.
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关键词
AMPKα,MiR-301a-3p,Non-small-cell lung cancer,Warburg effect,β-elemene
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