Circular RNA MYLK Promotes Glycolysis and Proliferation of Non-Small Cell Lung Cancer Cells by Sponging miR-195-5p and Increasing Glucose Transporter Member 3 Expression

Cancer Manag Res. 2020 Jul 7:12:5469-5478. doi: 10.2147/CMAR.S257386. eCollection 2020.

Abstract

Introduction: Circular RNAs (circRNAs) are deregulated in many types of human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functional role of circMYLK in NSCLC.

Materials and methods: The expression levels of circMYLK and miR-195-5p in NSCLC tissues and cell lines were detected by RT-qPCR analysis. MTT assay, colony formation assay and transwell assay were performed to investigate the effects of circMYLK and miR-195-5p on the malignant phenotypes of NSCLC cells. The glucose consumption and lactate production of NSCLC cells were detected using commercial kits. The direct binding relation between circMYLK and miR-195-5p in NSCLC was predicted by bioinformatics analysis and validated by dual-luciferase reporter assay.

Results: The results showed that circMYLK was significantly up-regulated in NSCLC tissues and cell lines, and its high expression was closely associated with deleterious clinicopathological characteristics and poor prognosis of NSCLC patients. Knockdown of circMYLK remarkably inhibited the malignant phenotypes of NSCLC cells, including proliferation, migration, invasion, glucose consumption and lactate production. Moreover, circMYLK was identified as a molecule sponge for miR-195-5p, and glucose transporter member 3 (GLUT3) was shown to be a target gene of miR-195-5p in NSCLC. Further rescue experiments revealed that the oncogenic effects of circMYLK on NSCLC cells could be largely abrogated by co-transfection with miR-195-5p mimic.

Conclusion: In summary, our study provides convincing evidence that circMYLK serves as a tumor promoter in NSCLC and can be used as a potential therapeutic target for NSCLC patients.

Keywords: circular RNA MYLK; glucose transporter member 3; glycolysis; miR-195-5p; non-small cell lung cancer.

Grants and funding

This work was supported by Chongqing Special Performance Incentive and Guidance Program for Scientific Research Institutions (Grant Nos. cstc2018jxj1130042 and cstc2018jxj1130045).