Background: Circular 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.
Methods: Cell 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.
Results: Circ_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.
Conclusion: Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR-924/SLC1A5 axis.
Keywords: SLC1A5; circ_0000463; glutamine metabolism; miR-924; non-small-cell lung cancer.
© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.