Xuebo Yan1, Tong Wang2, Jiong Wang1. 1. Department of Geriatric Respiratory and Critical Care, Institute of Respiratory Disease, Provincial Key Laboratory of Molecular Medicine for Geriatric Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 2. Department of General Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Abstract
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.
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.