Circ_0016760 Acts as a Sponge of MicroRNA-4295 to Enhance E2F Transcription Factor 3 Expression and Facilitates Cell Proliferation and Glycolysis in Non-Small Cell Lung Cancer.

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Background: Circular RNAs (circRNAs) have been validated as important regulators of non-small cell lung cancer (NSCLC), but the role and potential mechanism of circ_0016760 in NSCLC remain largely unclear. Materials and Methods: Quantitative real-time polymerase chain reaction was performed to detect the levels of circ_0016760, microRNA-4295 (miR-4295), and E2F transcription factor 3 (E2F3). The cell proliferation was measured by methyl-thiazolyl diphenyl-tetrazolium bromide assay. The protein levels of proliferating cell nuclear antigen and E2F3 were examined by Western blot. Xenograft mice model was constructed to explore the effect of circ_0016760 on tumor growth in vivo. The relationship among circ_0016760, miR-4295, and E2F3 was evaluated using dual-luciferase reporter assay. Glucose consumption of NSCLC cells was assessed by the glucose assay kit. Results: Circ_0016760 and E2F3 expression levels were upregulated in NSCLC tissues and cells, while miR-4295 was downregulated. Circ_0016760 could bind to miR-4295, and negatively modulate its expression in NSCLC cells. Besides, miR-4295 directly targeted E2F3 and inversely regulated E2F3 expression. More importantly, Circ_0016760 facilitated proliferation and glycolysis of NSCLC cells by increasing E2F3 by sponging miR-4295 as well as promoted the tumor growth in vivo. Conclusion: Circ_0016760 served as a growth-promoting circRNA in NSCLC by facilitating cell proliferation and glycolysis by regulating the miR-4295/E2F3 axis, providing a novel potential target for NSCLC treatment.