Downregulation of Hsa_circ_0000735 Inhibits the Proliferation, Migration, Invasion, and Glycolysis in Non-small-cell Lung Cancer by Targeting miR-940/BMPER Axis

摘要

Background: Lung cancer is the most commonly diagnosed cancer and the major cause of cancer-related deaths worldwide. The increasing studies have demonstrated that circular RNA (circRNA) was involved in the progression of various cancers, including non-small-cell lung cancer (NSCLC). This study was designed to assess the expression, roles and functional mechanisms of circ_0000735 in NSCLC. Materials and Methods: The expression levels of circ_0000735, miR-940 and bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER) were estimated by the real-time quantitative polymerase chain reaction (RT-qPCR). The biological behaviors of NSCLC cells such as proliferation, migration and invasion were analyzed by cell counting kit-8 (CCK-8), colony-forming assays and transwell assay, respectively. Furthermore, extracellular acid ratio and lactate production were tested to assess glycolysis levels of NSCLC cells. The interaction relationship among circ_0000735, BMPER and miR-940 was analyzed by bioinformatics database and dual-luciferase reporter assay. The protein expression level of BMPER was assessed by Western blot assay. Tumorigenesis assay was established to clarify the functional roles of circ_0000735 in vivo. Results: Circ_0000735 was upregulated and significantly correlated with overall survival in patients with NSCLC. In addition, the loss-of-functional experiments revealed that knockdown of circ_0000735 repressed proliferation, migration, invasion and glycolysis of NSCLC cells and tumor growth in vivo, which was overturned by overexpression of BMPER. Similarly, overexpression of circ_0000735 enhanced proliferation, migration, invasion, and glycolysis of NSCLC cells. In addition, we also confirmed that overexpression of miR-940 impeded proliferation, migration, invasion, and glycolysis of NSCLC cells. Furthermore, overexpression of BMPER abolished si-circ_0000735 induced effects on NSCLC cells. Conclusion: Circ_0000735 regulated proliferation, migration, invasion, and glycolysis in NSCLC cells by targeting miR-940/BMPER axis.