Circular RNA, Circular RARS, Promotes Aerobic Glycolysis of Non‐small‐cell Lung Cancer by Binding with LDHA

Purpose:Accumulating evidence has highlighted the critical roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC). This study aims to unveil the roles of circRARS (circular RARS) (hsa_circ_0001551) in NSCLC. Methods:Quantitative real-time PCR was used to determine the expression of circRARS in NSCLC tissues and cells. Kaplan-Meier analysis was used to determine the prognostic value of circRARS expression. CCK8, transwell, and wound healing assays were used to assess the proliferation, invasion, and migration abilities of NSCLC cells. RNA pull-down, cell fraction, glucose consumption, lactate production, and lactate dehydrogenase activity assays were conducted to explore the potential mechanisms of circRARS in NSCLC. Results:circRARS is upregulated in NSCLC tissues and positively correlated with smoking status, lymph node metastasis, and higher tumor stages. NSCLC patients with high expression of circRARS have poor overall survival. Functional assays demonstrated that circRARS accelerated the proliferation, invasion, and migration of NSCLC cells in vitro. The cell fraction suggested that circRARS mainly accumulated in cytoplasm and the RNA pull-down assay showed lactate dehydrogenase (LDHA) could bind with circRARS. Furthermore, circRARS positively regulates LDHA activity and LDHA expression at the transcription level. Moreover, downregulated circRARS decreases glucose consumption and lactate production and compromises aerobic glycolysis in NSCLC cells. Finally, rescue assays showed circRARS could promote NSCLC cell proliferation by regulating LDHA activity. Conclusion:This study shows that circRARS can promote glycolysis and tumor progression in NSCLC by regulating LDHA.