Circular RNA circ-ACACA regulates proliferation, migration and glycolysis in non-small-cell lung carcinoma via miR-1183 and PI3K/PKB pathway

Non-small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers and the five-year survival rate is ~1% in the late stage. Circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ-ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ-ACACA and microRNA (miR)-1183 in NSCLC tissues and cells. A Cell Counting Kit-8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3-kinases (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (PKB) and p-PKB in samples were measured by western blotting. The interaction between circ-ACACA and miR-1183 was predicted by circular RNA Interactome, which was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft tumor model was established to investigate the biological roles of circ-ACACA in vivo. The level of circ-ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expres-sion of miR-1183. Knockdown of circ-ACACA inhibited proliferation and migration of NSCLC cells and also reduced the glycolysis rate. In addition, miR-1183 was a target of circ-ACACA and its downregulation reversed circ-ACACA silencing-mediated inhibitory impact on NSCLC progression. Further studies indicated that circ-ACACA regulated the PI3K/PKB pathway through interacting with miR-1183 and downregulation of circ-ACACA suppressed tumor growth. Knockdown of circ-ACACA impeded NSCLC progression by sponging miR-1183 and inactivating the PI3K/PKB signaling pathway.