Abstract
The eukaryotic translation initiation factor 4A (eIF4A) family determines transcription efficiency by directly binding to precursor RNAs. One member, EIF4A3, modulates the expression of circRNAs. Circular RNA SCAP (circSCAP), a newly found circRNA, has been implicated in atherosclerosis. Yet, how circSCAP regulates cancer development and progression remains understudied. Here, we investigated the function of circSCAP and the molecular mechanism in the tumorigenesis and progression of non-small-cell lung cancer (NSCLC). CircSCAP was upregulated in both NSCLC tissues and cell lines and was mainly located in the cytoplasm. CircSCAP expression was promoted by EIF4A3, which was associated with poor prognosis in patients with NSCLC. CircSCAP sponged miR-7 to upregulate small mothers against decapentaplegic 2 (SMAD2). CircSCAP knockdown undermined cell proliferation, migration, and invasion abilities in NSCLC cell lines (SPCA1 and A549), which was rescued by either inhibiting miR-7 or overexpressing SMAD2. Moreover, circSCAP knockdown upregulated E-cadherin, while downregulating N-cadherin, Vimentin, and MMP9 in SPCA1 and A549 cells, which were abolished by either inhibiting miR-7 or overexpressing SMAD2. Additionally, miR-7 was markedly downregulated, whereas SMAD2 was significantly upregulated in NSCLC tissues. MiR-7 expression was inversely correlated with circSCAP and SMAD2 expression in NSCLC tissues. In conclusion, this study demonstrates that circSCAP is significantly upregulated in NSCLC cell lines and tissues and elucidates that circSCAP facilitates NSCLC progression by sponging miR-7 and upregulating SMAD2. The study provides a novel molecular target for early diagnosis and treatment of NSCLC.