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hsa_circ_0008758 Activates the MDM2/FOXO3a/PGK1 Pathway Through the miR-361-3p/SPIN1 Axis to Promote the Warburg
Lei Wei1,2, Fei Xu2, Lei Xiong2
1Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42, Baizi Pavilion, Nanjing City, 210009, Jiangsu Province, China.
Background:
The involvement of circRNAs in tumors, such as non-small cell lung cancer (NSCLC), has been established. The objective of this research was to examine the function and regulatory mechanism of hsa_circ_0008758 (circ_0008758) in NSCLC.
Methods:
The expression of circ_0008758 in NSCLC tissues and cell lines was evaluated by RT-qPCR. Cell proliferation was assessed using the CCK-8 assay and colony formation assay. Apoptosis was evaluated through flow cytometry. Cell migration was measured using the scratch test, while cell invasion was determined using the transwell assay. The Warburg effect was assessed by measuring glucose uptake and lactic acid production using commercially available kits. The targeting relationship between miR-361-3p and circ_0008758 or SPIN1 was confirmed through a bioinformatics website analysis and a dual-luciferase reporter assay. The MDM2/FOXO3a/PGK1 pathway was examined by Western blot analysis.
Results:
circ_0008758 expression was augmented in NSCLC. Inhibiting circ_0008758 or elevating miR-361-3p resulted in decreased proliferation, migration, invasion, and Warburg effect in NSCLC cells, while promoting cell apoptosis. The opposite effect could be obtained by up-regulating circ_0008758 or down-regulating miR-361-3p. Furthermore, circ_0008758 was found to enhance SPIN1 expression by acting as a sponge for miR-361-3p. Up-regulating SPIN1 counteracted the effects of circ_0008758 down-regulation on NSCLC cells. Additionally, circ_0008758 was found to activate the MDM2/FOXO3a/PGK1 pathway by the miR-361-3p/SPIN1 axis.
Conclusion:
circ_0008758 promotes the Warburg effect in NSCLC through the miR-361-3p/SPIN1 axis and by activating the MDM2/FOXO3a/PGK1 pathway.
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