Circ_0000463 contributes to the progression and glutamine metabolism of non-small-cell lung cancer by targeting miR-924/SLC1A5 signaling.

Abstract

BackgroundCircular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non‐small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated.MethodsCell proliferation ability was analyzed by colony formation assay and 5‐ethynyl‐2’‐deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA‐924 (miR‐924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α‐ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth.ResultsCirc_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR‐924, and circ_0000463 interference‐mediated anti‐tumor effects were largely reversed by the silence of miR‐924 in NSCLC cells. miR‐924 interacted with the 3’ untranslated region (3’UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR‐924 overexpression‐mediated anti‐tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR‐924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo.ConclusionCirc_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis.