Circular RNA ATP9A Stimulates Non-small Cell Lung Cancer Progression via MicroRNA-582-3p/Ribosomal Protein Large P0 Axis and Activating Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway.

Abstract

Circular RNAs (circRNAs), along with their pathogenic property in non-small cell lung cancer (NSCLC), require comprehensive analyses and explanations. The study is established with the purpose to elucidate the potential molecular mechanism of circATP9A in NSCLC. CircATP9A and microRNA (miR)-582-3p were evaluated by real-time quantitative polymerase chain reaction, and ribosomal protein large P0 (RPLP0), cleaved caspase-3, cleaved Ki-67, epithelial-to-mesenchymal transition (EMT)-associated proteins (N-cadherin and E-cadherin), and core proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were by Western blot. The processes of proliferation, apoptosis, migration, and invasion were measured by cell counting kit-8, 5-ethynyl-2'deoxyuridine, flow cytometry, and Transwell. Gene interaction was verified by RNA immunoprecipitation and dual luciferase reporter assay. CircATP9A and RPLP0 were abnormally highly expressed in both NSCLC tissues and cell lines, while miR-582-3p was abnormally low. Knockdown of circATP9A reduced NSCLC proliferation, invasion migration, and EMT and promoted apoptosis. This was further validated in nude mouse xenograft experiments. The inhibitory effect of knockdown of circATP9A on NSCLC was reversed by knockdown of miR-582-3p. In addition, the promoting effect of overexpression of circATP9A on NSCLC was reversed by knockdown of RPLP0. Mechanistically, circATP9A acted as a competitive endogenous RNA, sequestering miR-582-3p away from its target, which in turn modulated the expression of RPLP0. CircATP9A activated the miR-582-3p/RPLP0 axis by regulating the PI3K/Akt pathway in NSCLC cells. CircATP9A stimulates NSCLC progression via miR-582-3p/RPLP0 axis and PI3K/AKT cascade activation.