Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT)

Abstract

Background: Previous studies have reported the role of circular RNAs (circRNAs) in the progression of non-small-cell lung cancer (NSCLC). SWT1-derived circRNAs were confirmed to affect the apoptosis of cardiomyocytes; however, the biological functions of SWT1-derived circRNAs in cancers are still unknown. Here, we investigated the potential role of SWT1-derived circRNAs in NSCLC.

Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of circSWT1 in NSCLC tissues and paired normal tissues. The potential functions of circSWT1 in tumor progression were assessed by CCK-8, colony formation, wound healing, and matrigel transwell assays in vitro and by xenograft tumor models in vivo. Next, epithelial-mesenchymal transition (EMT) was evaluated by western blotting, immunofluorescence, and immunohistochemistry (IHC). Moreover, circRIP, RNA pulldown assays, luciferase reporter gene assays, and FISH were conducted to illuminate the molecular mechanisms of circSWT1 via the miR-370-3p/SNAIL signal pathway. Then, we knocked out SNAIL in A549 and H1299 cells to identify the roles of circSWT1 in the progression and EMT of NSCLC through SNAIL. Finally, circSWT1 functions were confirmed in vivo using xenograft tumor models.

Results: CircSWT1 expression was significantly upregulated in NSCLC tissues, and high expression of circSWT1 predicted poor prognosis in NSCLC via survival analysis. In addition, overexpression of circSWT1 promoted the invasion and migration of NSCLC cells. Subsequently, we found that overexpression of circSWT1 induced EMT and that knockdown of circSWT1 inhibited EMT in NSCLC cells. Mechanistically, circSWT1 relieved the inhibition of downstream SNAIL by sponging miR-370-3p. Moreover, we found that these effects could be reversed by knocking out SNAIL. Finally, we verified that circSWT1 promoted NSCLC progression and EMT in xenograft tumor models.

Conclusion: CircSWT1 promoted the invasion, migration, and EMT of NSCLC. CircSWT1 could serve as a potential biomarker and a potential therapeutic target for NSCLC.

Keywords: EMT; NSCLC; SNAIL; circSWT1; invasion and metastasis.