Background: Circular RNAs (circRNAs) have recently been shown as important regulators in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this work was to explore the precise parts played by circRNA SEC31 homolog A (circSEC31A, hsa_circ_0001421) in NSCLC malignant progression.
Methods: The expression levels of circSEC31A, miR-376a and SEC31 homolog A (SEC31A) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Subcellular fractionation assay was used to determine the subcellular localization of circSEC31A, and RNase R assay was performed to assess the stability of circSEC31A. Cell migration and invasion were detected by transwell assay, and cell apoptosis was evaluated using flow cytometry. Measurement of glucose consumption, lactate production and adenosine triphosphate (ATP) level were done using corresponding assay kits. The targeted interactions among circSEC31A, miR-376a and SEC31A were confirmed by the dual-luciferase reporter and RNA pull-down assays. Animal studies were performed to observe the role of circSEC31A in tumor growth in vivo.
Results: Our data indicated that circSEC31A and SEC31A were upregulated in NSCLC tissues and cells. CircSEC31A knockdown suppressed NSCLC cell migration, invasion, glycolysis and promoted apoptosis in vitro, as well as hindered tumor growth in vivo. Mechanistically, circSEC31A directly interacted with miR-376a, and circSEC31A depletion regulated NSCLC cell malignant progression by miR-376a. Moreover, SEC31A  was a functional target of miR-376a, and it mediated the regulatory impact of miR-376a overexpression on NSCLC cell progression. Furthermore, circSEC31A controlled SEC31A expression through acting as a miR-376a sponge.
Conclusion: Our findings first identified that the knockdown of circSEC31A suppressed NSCLC malignant progression at least partly through modulating SEC31A expression by acting as a miR-376a sponge, providing a novel molecular target of NSCLC therapy.
Keywords: NSCLC, circSEC31A, miR-376a, SEC31A, malignant progression