MicroRNA-6077 enhances the sensitivity of patients-derived lung adenocarcinoma cells to anlotinib by repressing the activation of glucose transporter 1 pathway

Abstract

Anlotinib is a novel molecular targeted agent targeting the vascular endothelial growth factor receptor, which differs from the other currently available non-small cell lung cancer (NSCLC) molecular targeted drugs targeting this receptor. Although the application of anlotinib may bring new hope for patients with advanced NSCLC, the cost of treatment is high. The results of this study showed that microRNA-6077 (miR-6077) represses the expression of GLUT1 (glucose transporter 1) and enhances the sensitivity of patient-derived lung adenocarcinoma (AC) cells to anlotinib. The miR-6077, which potentially binds to the 3’untranslated region of GLUT1, was identified and screened by miRDB, an online tool; sequences of miR-6077 were prepared as lentivirus particles. A549 cells (a lung adenocarcinoma cell line) and five patient-derived AC cell lines were infected with control miRNA or miR-6077, and subsequently treated with the indicated concentration of anlotinib. The expression of proteins, such as GLUT1, was determined by western blotting. The antitumor effect of anlotinib was identified through in-vitro (e.g., MTT) or in-vivo methods (e.g., subcutaneous tumor model). Overexpression of miR-6077 repressed the expression of GLUT1 and decreased the glucose uptake, lactate production, or ATP generation in AC cells. In addition, MiR-6077 may enhance the antitumor effect of anlotinib on A549 or patient-derived AC cell lines. Therefore, our results indicated that miR-6077 represses the expression of GLUT1 and enhances the sensitivity of patients-derived lung AC cells to anlotinib.